COHA Translational Fellowship Opportunity for Residency-Trained Veterinary Specialists
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COHA Translational Fellowship Opportunity
for Residency-Trained Veterinary Specialists
Title of fellowship focus: Exploring the use of immune regulatory cells to enable successful allogeneic solid
organ transplant and adoptive T cell therapy in companion animals
Area of Research: This fellowship will focus on exploring the immune regulatory (IR) properties of canine
regulatory T cells (Tregs) and iNKT cells in vitro and on evaluating the effects of ex vivo activated and
expanded IR cells to enable successful allogeneic canine renal transplant or allogeneic off-the-shelf adoptive T
cell therapies for dogs with hematological cancers.
University/Department: University of Pennsylvania, School of Veterinary Medicine, Clinical Sciences and
Advanced Medicine
Primary Mentor: Nicola Mason BVetMed, PhD (immunology), DACVIM (internal medicine), Professor of
Medicine; nmason@vet.upenn.edu
Mentor Team (all within the School of Veterinary Medicine, University of Pennsylvania)
Research arm of mentor team:
Raimon Duran-Struuck DVM, PhD (immunology) Diplomate ACLAM. Assistant Professor & Director of
Scientist Regulatory Support and Laboratory Animal Medicine Residency Training Program. University
Laboratory Animal Resources.
Antonia Rotolo MD (Internal Medicine, Fellowship in Hematopoietic Stem Cell Transplantation at Imperial
College London, UK) PhD (Immunology) Post-doctoral fellow.
Clinical arm of mentor team:
Lily Aronson VMD, Diplomate ACVS, Professor of Surgery, Director of Renal Transplantation services
Katie Mauro DVM, Diplomate ACVECC, Assistant Professor of Clinical Extracorporeal Therapies
Description of Potential Research Project(s)
Rejection of major histocompatibility unmatched, allogeneic tissues and cells is a significant barrier to
successful organ transplant and off-the-shelf, genetically engineered adoptive T cell therapies. Overcoming this
barrier by exploiting the beneficial effects of immune regulatory cells would enable more patients to receive
life-saving organ transplants or adoptive T cell therapies that have the potential to cure patients with
hematological and solid cancers. Here, we propose a translational research project that will leverage the on-
campus expertise of translational immunologists, transplant immunologists and surgeons and extracorporeal
therapy criticalists to explore the use of adoptive transfer of immune regulatory cell types such as regulatory T
cells (Tregs) and iNKT cells to promote immune tolerance. Our group has significant expertise in transplant
immunology and renal transplant surgery and in the generation and use of adoptive cellular therapies in canine
cancer patients. Our goal is to apply our combined expertise to develop canine immune regulatory cellular
therapies that can be used either alone or in combination with other immunomodulatory platforms to enable
successful allogeneic renal transfer in canines with chronic renal failure as well as adoptive transfer of off-the-
shelf, genetically engineered allogeneic T cell products for dogs with spontaneous hematological cancers. Our
labs are supported by federal and private foundation grants and the close proximity of the veterinary andmedical schools on the same university campus will enable the successful fellow to participate in the many
different seminars, research symposia, journal clubs and lab meetings offered to members of the Penn
community.
Additional Training Opportunities
The University of Pennsylvania is located in University City, in West Philadelphia. The Schools of
Medicine and Veterinary Medicine are located within a 10 minute walk of each other and boast a highly
collaborative and well connected community that includes some of the most prominent immunologists, including
transplantation immunologists, translational cancer immunotherapists and transplantation surgeons in the country.
On the clinical/translational side, the School of Veterinary Medicine has one of the most successful renal
transplant programs in the country which is supported by a well-integrated extracorporeal therapy unit that serves
both the clinical and research communities. The successful candidate will be fully supported by their mentors and
will have full access to all the training opportunities that can be found on campus to advance their knowledge
and education. Collectively the Institute for Immunology (IFI), the Center for Cellular Immunotherapies (CCI),
the Institute for Translational Medicine And Therapeutics (ITMAT) and the Penn Institute for Bioinformatics
provide a wealth of seminars, workshops, research retreats, journal clubs and grant writing courses that the
successful candidate can benefit from. Furthermore, relevant, graduate level statistical and bioinformatics courses
will also be on offer. Fellows will have the opportunity to spend up to 25% of their time performing clinical/
translational work in their specialty area. They will also be encouraged to present their work at institutional,
local and international meetings to gain exposure to the community, experience in presenting their work and to
build collaborations.
Fellowships are for 2 years and provide stipend and employee benefits at the NIH post-doctoral pay scale.
Fellows may supplement their stipend with up to 25% effort towards clinical work, if such work is in alignment
with the research and career development plan.
All fellowships will have a start date of fall 2021.
Biosketches of primary mentor and mentor team - please find attached.OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Mason, Nicola J.
eRA COMMONS USER NAME (credential, e.g., agency login): NJMASON
POSITION TITLE: Associate Professor of Medicine
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
DEGREE Completion
(if Date FIELD OF STUDY
INSTITUTION AND LOCATION
applicable) MM/YYYY
Royal Veterinary College, University of London, UK B.Vet. Med. 06/1992 Veterinary Medicine
School of Veterinary Medicine, University of PhD 06/2004 Immunology
Pennsylvania, USA
School of Medicine, University of Pennsylvania, USA Postdoctoral 06/2006 Translational
Fellow Immunology
A. Personal Statement
I am a veterinarian with board certification in internal medicine. My translational research program has focused
on a comparative approach, utilizing immunologically intact, canine patients with spontaneous cancer in clinical
trials to advance immunotherapeutics for use in children and adults with cancer. Certain cancers that occur
spontaneously in dogs exhibit remarkable biological, behavioral and genetic similarities to those that occur in
human patients. Furthermore, through our work and that of others, we have also recognized comparable barriers
to effective immunotherapy in the dog which include T cell exclusion, T cell exhaustion, antigen escape via
epitope splicing and tumor microenvironment components such as MDSC, Tregs and inhibitory cytokines that
contribute to ineffective T cell therapies. Finally, unlike many murine models, canine patients are immunologically
intact, a feature that is particularly relevant to evaluating the safety of increasingly potent immunotherapeutic
strategies. Thus, dogs with spontaneous cancer provide a unique opportunity to evaluate the safety and
effectiveness of next generation immunotherapies that can then be fast-tracked into the human clinic.
I performed my postdoctoral research in the laboratory of Dr. Carl June where I began work to develop systems
that would enable us to evaluate CAR T cell therapies in dogs. Since then, I have successfully translated novel
immunotherapies to generate anti-tumor immunity from the lab and pre-clinical murine models into client owned
dogs suffering from lymphoma, osteosarcoma and hemangiosarcoma. I have been actively involved in evaluating
the immunological consequences of immune–based therapies in client owned dogs for over 10 years and have
extensive experience in flow cytometric phenotyping of canine T cells and functional assays to investigate canine
T cell responses. Most recently, my lab has become primarily focused on advancing our CART cell therapy
program. We have developed apheresis protocols, T cell activation and expansion protocols, efficient
transduction protocols and pre-conditioning regimes that have led to the first clinical canine CAR T cell therapy
trial in the country. We are uniquely situated adjacent to the University of Pennsylvania’s School of Medicine
where many of our collaborators have their labs and clinics. One of the holy grails of CAR T cell therapy is the
ability to utilize allogeneic CAR T cells taken from a healthy individual, to overcome the intrinsic dysfunction of
autologous T cells from patients with cancer. In this proposal we aim to leverage the natural immunoregulatory
properties of Tregs and iNKT cells to enable successful allogeneic transplant of both adoptive T cell therapies
for cancer and kidneys for chronic renal failure in dogs.
B. Positions and Honors
Positions and Employment1992-1993 Assistant Veterinarian, Broadway Veterinary Clinic, Peterborough, UK.
1993-1995 Medical Internship (small animal), University of Bristol, UK.
1995-1997 Medical Residency (small animal), University of Pennsylvania, School of Vet. Med. USA.
1997-2000 Lecturer in Small Animal Internal Medicine, University of Pennsylvania, School of Vet. Med.
2000-2003 Research Associate, University of Pennsylvania, School of Vet. Med. USA.
2003-2006 Senior Research Investigator, University of Pennsylvania, School of Medicine, USA.
2006-2015 Assistant Professor in Clinical Studies, University of Pennsylvania, School of Vet. Med. USA.
2015- Associate Professor in Clinical Studies, University of Pennsylvania, School of Vet. Med. USA.
Other Experience and Professional Memberships
1998-present Member – American College of Veterinary Internal Medicine
2007-present Member – Immunology Graduate Group, University of Pennsylvania
2007-present Associate Director (translational research), Mari Lowe Comparative Oncology Center, University
of Pennsylvania, School of Vet. Med. USA
2008-present Member – Cell and Molecular Biology Graduate Group, University of Pennsylvania (Member of
the Student Selection Committee)
2010-present Abramson Cancer Center
2010-present ITMAT member
2010-present Member – American Association of Veterinary Immunologists
2011-present Member – American Society of Microbiology
2012-present Member – Veterinary Cancer Society
2012-present Scientific Advisory Board of the Skippy Frank Translation Medicine Foundation
2013-present Scientific Advisory Board of the National Canine Cancer Foundation
2016-present Scientific Advisory Board of the Morris Animal Foundation
2016-present Scientific Advisory Board of Canines N’ Kids Foundation
2016-present Scientific Advisory Board of the One Health Company
2016-present Member - Parker Institute for Cancer Immunotherapy
Honors
1997 Pfizer Distinguished Research Award -American College of Veterinary Internal Medicine
1998 Diploma in Small Animal Internal Medicine, American College of Veterinary Internal Medicine
2006 Merck-Merial Young Investigator Award- National Veterinary Scholars Award
2013 Inaugural One Health Award (a new Award for Excellence in promoting One Health Initiatives and
Interprofessional Education at the University of Pennsylvania) received together with Dr. Yvonne
Paterson Professor of Microbiology, Perelman School of Medicine, Professor of Nursing &
Associate Dean for Research, School of Nursing
2018 Paul A. James and Charles A. Gilmore Endowed Chair Professorship
2018 Zoetis Award for Veterinary Research Excellence
2018 NIH Directors Transformative Research Award (R01)
C. Contribution to Science
Demonstration of robust methods to expand and genetically modify canine T cells with chimeric
antigen receptors ex vivo and evaluate the safety and therapeutic effect of canine CAR T cells in vivo.
Preclinical murine models of chimeric antigen receptor (CAR) T cell therapy are widely applied but are greatly
limited by their inability to model the complex human tumor microenvironment and adequately predict safety
and efficacy in patients. We therefore developed an expansion methodology that yields high numbers of canine
T cells from normal or lymphoma-diseased dogs. mRNA electroporation or lentiviral transduction was utilized
to express a first or second generation canine CD20-specific CAR in expanded T cells. cCD20 CAR T cells
exhibited antigen-specific IFN-γ secretion and lysed cCD20+ targets. In a first-in-canine study, autologous
cCD20-CD28- CAR T cells were administered to dogs with relapsed B cell lymphoma. Treatment was well
tolerated. Two dogs showed clear evidence of target antigen modulation following CAR T cell therapy with one
patient exhibiting antigen-escape via epitope splicing. Canine anti-mouse antibodies developed and coincided
with loss of CAR T cell detection in vivo. This work establishes the methodologies necessary to evaluate CAR
T cell therapy in dogs with spontaneous malignancies, outlines comparable barriers to effective treatment as
seen in human patients and lays the foundation for the use of outbred canine cancer patients to evaluate the
safety and efficacy of next-generation CAR therapies and their optimization prior to translation into humans.a. Panjwani MK, Smith JB, Schutsky K, Gnanandarajah J, O’Connor C, Powell DJ, Mason NJ. Feasibility
and safety of RNA-transfected CD20-specific Chimeric Antigen Receptor T cells in dogs with
spontaneous B cell lymphoma. Mol Ther. 2016 Sep;24(9):1602-14.
b. Yin Y, Boesteanu AC, Binder ZA, Xu C, Reid RA, Rodriguez JL, Cook DR, Thokala R, Blouch K,
McGettigan-Croce B, Zhang L, Konradt C, Cogdill AP, Panjwani MK, Jiang S, Migliorini D, Dahmane N,
Posey AD Jr, June CH, Mason NJ, Lin Z, O'Rourke DM, Johnson LA. Checkpoint Blockade
Reverses Anergy in IL-13Rα2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine
Gliomas. Mol Ther Oncolytics. 2018 Aug 28;11:20-38.
c. Atherton MJ., Panjwani KP., MaloneyHuss MA., Haran KP., Xiong A., Gupta N., Kulikovsaya I., Lacey
SF., Mason NJ. Establishing a model system for evaluating CAR T cell therapy in dogs with spontaneous
diffuse large B cell lymphoma (accepted to OncoImmunology)
Demonstration that CD40 activated B cells can be used as an alternative to Dendritic Cells to generate
autologous cancer vaccines that stimulate anti-tumor immunity and improve second remission in dogs
with spontaneous lymphoma. While autologous dendritic cell cancer vaccines have been shown to break
tolerance to self-antigens and induce anti-tumor immune responses that can lead to improved outcomes in
human cancer patients, they suffer from significant manufacturing issues. One main issue is the requirement
for large volume apheresis to secure sufficient progenitor cells to make a viable product. We have shown that
B cells can be activated and expanded from a small volume of peripheral blood taken from healthy dogs and
dogs with spontaneous lymphoma. We have shown that these cells can be loaded with autologous tumor RNA
and used to expand antigen-specific T cells in vitro, in a similar manner to dendritic cells, without the need for
large volume leukapheresis. Furthermore, we have shown that RNA loaded CD40-activated B cells can be
used in vivo, in dogs with spontaneous lymphoma, following successful induction chemotherapy to induce
tumor specific immune responses and increase second remission times. Taken together, our work has been
the first to describe the use of CD40-activated B cells in a clinical trial setting using dogs with spontaneous
lymphoma to evaluate its effects on tumor-specific immunity and long-term outcome. The work outlined in aims
2 and 3 will utilize these techniques for evaluating immunogenicity of non-synonymous mutations.
a. Mason NJ, Coughlin C, Colligan T., Cohen J., Mitchell E., Overley E., Clifford C., Sorenmo K.,
Vonderheide R. RNA-loaded CD40-activated B cells stimulate antigen-specific T cell responses in dogs
with spontaneous lymphoma. Gene Therapy 2008; 15(13):955-65.
b. Sorenmo KU, Krick E., Coughlin CM, Overley E, Gregor TP, Vonderheide RH, Mason NJ. CD40-
activated B cell cancer vaccine improves second clinical remission and survival in privately owned dogs
with non-Hodgkin’s lymphoma PLoS One. 2011;6(8):e24167. Epub 2011 Aug 31.
c. Ito D., Frantz A., Williams C., Thomas R., Burnett RC., Avery A., Breen M., Mason NJ., O’Brien T.,
Modiano J. CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma
cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies. Leuk Lymphoma.
2012 Jul;53(7):1390-8. Epub 2012 Feb 3.
Demonstration that recombinant Listeria expressing a chimeric human HER2/neu can safely break
tolerance to HER2 and delay or prevent metastatic disease in a spontaneous model of osteosarcoma.
Treatment of pediatric osteosarcoma consists of neoadjuvant chemotherapy, radiotherapy and radical surgery.
Despite treatment, metastatic disease is common and results in mortality rates of 30-40% within 5 years of
diagnosis. To evaluate novel strategies to prevent metastatic disease, we have turned to the canine
osteosarcoma patient. Canine osteosarcoma recapitulates many aspects of pediatric osteosarcoma, including
high genetic instability and histologic heterogeneity, the aggressive local disease, early metastases and
comparable surgical, chemotherapeutic and radiation treatment options. Approximately 90-95% of dogs have
micrometastases at diagnosis. The high incidence of micrometastases coupled with standard of care
amputation and chemotherapy, make dogs with spontaneous OSA ideal candidates in which to evaluate the
safety and efficacy of immune therapies, administered in the setting of minimal residual disease, to prevent
metastatic disease and inform human clinical trials.
HER2/neu is expressed in 40% of pediatric OSA, where it is linked to reduced response to neoadjuvant
chemotherapy, high metastatic rates and shorter overall survival times. Recent reports also suggest that
HER2/neu is expressed on cancer stem cells in both OSA and mammary carcinoma and that HER2/neu
targeted immune therapies may eliminate these cells and prolong overall survival in both tumor types. We have
performed a clinical trial to evaluate the safety and efficacy of ADXS31-164, a highly attenuated recombinantListeria monocytogenes expressing a chimeric human HER2/neu construct, to induce HER2/neu specific
immunity and prevent metastatic disease in dogs with appendicular OSA following amputation and
chemotherapy. We have shown that ADXS31-164 administration, in the setting of minimal residual disease, is
safe in dogs, breaks peripheral tolerance to HER2/neu and prolongs survival by delaying or preventing
metastatic disease. Our findings represent a major advance in the search for more potent therapeutics aimed
at preventing metastatic OSA and have important implications in pediatric osteosarcoma, HER2/neu + breast
cancer and other human and canine HER2/neu expressing neoplasms.
a. Mason NJ, Gnanandarajah J, Engiles J, Gray F, Laughlin D, Gaurnier-Hausser A, Wallecha A,
Huebner M, Paterson Y. Immunotherapy with a HER2 targeted Listeria induces HER2-specific
immunity and demonstrates potential therapeutic effects in a phase I trial in canine osteosarcoma. Clin
Cancer Res. 2016 Sep 1;22(17):4380-90
Complete List of Published Work in My Bibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/18Ii8ys6JGwAv/bibliography/46382630/public/?sort=date&direction=a
scending.
D. Research Support
ACTIVE (Selected awards shown only)
U54CA244711-01 Mason (co-PI of project 2) 9/1/2019-8/31/2024
NIH/NCI
Engineering the next generation of T cells
Major goals: to develop genetically engineered allogeneic CAR T cell therapies that may serve as an off-the-
shelf product for treating patients with solid and hematological malignancies. In Project 2, we will explore the
barriers that exist to successful xenogenic transfer of CAR T cells using canine CD20-targeting, CRISPR
edited human CAR T cells in canine patients with B cell malignancies. The aim is to leverage canines with
spontaneous disease to evaluate mechanisms to enable allogeneic transfer in human cancer patients.
V Foundation Mason (co-PI) 10/1/2019-9/30/2021
Unravelling mechanisms of resistance to immune checkpoint inhibition in canine urothelial carcinoma
The main goals of this award are to characterize the tumor mutational burden in canine invUC and correlate
this with the tumor immunome, to evaluate clinical and immunological responses to ICI in dogs with invUC and
to determine which features of the immune landscape, tumor and/or microenvironment that underlie
responsiveness to checkpoint inhibition.
R01-ODO26202-01 Mason (co-PI) 9/1/2018-8/31/2023
NIH/NCI
Translating cellular immunotherapies for autoimmunity to canine clinical trials
Major Goals: We recently developed a novel gene-engineered cellular immunotherapy that has the potential to
cause complete and lasting remission of autoimmune disease. To pave the way for first-in-human trials, we will
now establish dogs with spontaneous autoimmune disease as a higher preclinical standard for establishing
safety and efficacy of cellular immunotherapy compared to using mice with artificially induced disease.
U24-CA224122 Mason (co-PI) 9/1/2017-8/31/2022
NIH/NCI
Coordinating Center for Canine Immunotherapy Trials and Correlative Studies
Major Goals: The primary goal is to develop a coordinating center for canine immunotherapy trials and
correlative studies that aims to provide infrastructure and oversight to a highly collaborative and interactive
network of researchers and clinician scientists working to investigate immunotherapeutic strategies in dogs
with cancer and identify correlates of immunological and therapeutic responses that will inform human clinical
trial design.OMB No. 0925-0001 and 0925-0002 (Rev. 03/2020 Approved Through 02/28/2023)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Duran-Struuck, Raimon
eRA COMMONS USER NAME (credential, e.g., agency login): RDSTRUUCK
POSITION TITLE: Assistant Professor of Pathobiology and Associate Director Laboratory Animal Resources.
University of Pennsylvania
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
DEGREE Completion
(if Date FIELD OF STUDY
INSTITUTION AND LOCATION
applicable) MM/YYYY
Tufts University, Boston, MA BS 1993-1998 Biochemistry
Tufts University, Boston, MA DVM 1998-2002 Veterinary Medicine
Florida Veterinary Specialists and Cancer Intern 2002-2003 Internal Medicine and Surgery
Treatment Center, Tampa, FL
University of Michigan School of Medicine, Residency 2003-2006 Laboratory Animal Medicine
Ann Arbor, MI
University of Michigan School of Medicine, Fellowship 2004-2007 Transplant Immunology
Ann Arbor, MI
Massachusetts General Hospital/Harvard Fellowship 2007-2010 Transplant Immunology
University, Boston, MA
Universitat Autonoma de Barcelona PhD 2005-2011 Immunology
A. Personal Statement
I am the director of the University of Pennsylvania Residency Training Program in Laboratory Animal Medicine
and been a clinical and research mentor of over twenty DVM/PhD/MS graduate students. I will be directly
involved in mentoring the COHA fellow on regulatory T cell biology and therapies for use in the clinic. I am a
cellular/transplant immunologist and clinical laboratory animal veterinarian. My research for the past 15 years
has focused in alloimmunity in both the fields of hematopoietic cell (HCT)and solid organ transplantation
(SOT). I have investigated cellular and molecular approaches to mitigate alloresponses with the goal to
improve transplant outcomes using pre-clinical large animals. In addition to my training as a clinical laboratory
animal veterinarian I have a PhD in transplant immunology and been fortunate to learn from clinical/research
physicians experts in transplantation (Drs Pavan Reddy, Jamie Ferrara, Markus Mapara, David Sachs,
Christene Huang, Thomas Spitzer, Megan Sykes). This has uniquely positioned me to develop and test novel
therapies in animal models with outcomes that closely mimic patients in the clinic. I have used NHPs and
swine models for the induction of solid organ transplant tolerance and methods to modulate GVHD using novel
cellular and pharmacological immunotherapies. Since 2012 I have been focused on the immunobiology and
translational use of polyclonal regulatory T cells and currently we are designing antigen specific CAR Tregs in
monkeys, swine and currently dogs. I have recently been studying nitric oxide for the modulation of
inflammation. As a laboratory animal veterinarian I have a deep understanding of the clinical needs of
debilitated animals undergoing transplant. I have developed expertise in the care of severely immunodeficient
animals. I also have a deep understanding of the research regulations achieving important clinical endpoints
while maintaining the welfare of animals and without terminating studies early. I have in vitro and in vivoexpertise in T cell (and regulatory T cell) biology. I have employed T cell functional assays, analytics including
multi-parameter flow cytometry, bioluminescent imaging, multiplex cytokine analysis and cell culture in multiple
species.
B. Positions and Honors
Employment:
2002-2003 Intern, Internal Medicine and Surgery, Florida Veterinary Specialists and Cancer Treatment
Center. Tampa, FL
2005-2007 Relief Veterinarian, Whittaker Road Animal Hospital, Ypsilanti, MI
2003-2007 Resident in Laboratory Animal Medicine/Comparative Medicine, Unit for Laboratory Animal
Medicine (ULAM), University of Michigan School of Medicine, Ann Arbor, MI
2004-2007 Post-doctoral Research Fellow, Bone Marrow Transplantation Laboratories, Department of
Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI
2007-2010 Post-doctoral Research Fellow, Transplantation Biology Research Center, Massachusetts
General Hospital, Harvard Medical School, Boston, MA
2010-2012 Assistant in Immunology, Transplantation Biology Research Center, Massachusetts General
Hospital, Boston, MA
2010-2012 Instructor in Surgery, Harvard Medical School, Boston, MA
2010-2012 Clinical Instructor (adjunct) Tufts University School of Veterinary Medicine
2012- 2015 Assistant Professor, Dept. of Surgery, Columbia University Medical Center.
2012- Clinical Assistant (adjunct) Professor. Tufts University School of Veterinary Medicine.
2015- Assistant Professor (Pathobiology) University of Pennsylvania School of Veterinary Medicine.
Associate Director of University Laboratory Animal Resources University of Pennsylvania.
Honors:
2006 Honorable Mention, Merck-Merial Young Investigator Award
2005-2007 Ad-hoc Reviewer Journal of Veterinary Parasitology
2007- Ad-hoc Reviewer Journal of the American Association of Laboratory Animal Science
2009- Ad-hoc Reviewer of Journal Transplantation
2009 Travel Award. American Society of Hematology. San Francisco, CA.
2011 Scientific Abstract Review Committee. American Association for Laboratory Animal Science.
San Diego 2011.
2011 Summa Cum Laude. PhD Thesis (Immunology). Universitat Autonoma de Barcelona.
Barcelona, Spain.
2012 Diplomate of the American College of Laboratory Animal Medicine
2012 Outstanding Alumnus Award. Tufts University School of Veterinary Medicine.
2013 American Association of Immunologists Travel Award. Boston. July.
2015 Associate Editor of Journal Comparative Medicine
2015 Associate Editor Journal of the American Association of Laboratory Animal Science
2016 Universitat Autonoma de Barcelona – Extraordinary Award in Advanced Immunology
2019 Leslie Brent Award. International Transplantation Society for the most outstanding manuscript in
Basic Science published in the journal Transplantation.
Professional Societies:
1998- American Veterinary Medical Association (AVMA)
2002- American Association of Laboratory Animal Science (AALAS)
2002- American Association of Laboratory Animal Practitioners (ASLAP)
2006- American Society for Transplantation and Cellular Therapy (ASTCT)
2013- American Society of Hematology (ASH)
2013- American Society of Transplantation (AST)
2014- Federation of Clinical Immunological Societies (FOCIS)
C. Contributions to Science
1) Approaches to mitigate GVHD and improve transplant outcomes with mega-HCT doses; I have
studied co-stimulatory (immune semaphorins) pathways in mice to prevent GVHD. I also developedreduced intensity preparatory regimens followed by mega-dose HCT’s for the induction of mixed
chimerism without GVHD in swine as a pre-clinical animal model.
1. Duran-Struuck R, Tawara I, Lowler K, Clouthier SG, Weisiger E, Rogers C, Luker G, Kumanogoh
A, Liu C, Ferrara JL, Reddy P. “A novel role for the semaphorin Sema4D in the induction of allo-
responses”. Biol Blood Marrow Transplant. 2007 Nov;13(11):1294-1303. PMCID: PMC2278022
2. Duran-Struuck R, Matar A, Crepeau R, Gusha A, Schenk M, Hanekamp I, Pathiraja V, Spitzer TR,
Sachs DH, Huang CA. “Lack of antidonor alloantibody does not indicate lack of immune
sensitization: studies of graft loss in a haploidentical hematopoietic cell transplantation Swine
model.” Biol Blood Marrow Transplant. 2012 Nov;18(11):1629-37 PMCID: PMC3575102
3. Matar AJ, Patil AR, Al-Musa A, Hanekamp I, Sachs DH, Huang CA, Duran-Struuck R. Effect of
Irradiation on Incidence of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell
Transplantation in Miniature Swine. Biol Blood Marrow Transplant. 2015
4. Duran-Struuck R, Matar AJ, Crepeau RL, Teague AGS, Horner BM, Pathiraja V, Spitzer TR,
Fishman JA, Bronson RT, Sachs DH, Huang CA.”Donor Lymphocyte Infusion-Mediated Graft-
versus-Host Responses in a Preclinical Swine Model of Haploidentical Hematopoietic Cell
Transplantation”. Biol. Bone Marrow Transplant 2016. Nov;22(11):1953-1960
2) Biology and Role of regulatory T cell therapies for immunological tolerance: I have studied the
biology of Tregs, developed protocols for and tested the expansion of polyclonal regulatory T cells
aimed to induce robust mixed hematopoietic cell chimerism without GVHD to prevent SOT rejection in
large pre-clinical animal models.
1. Weiner J, Duran-Struuck R, Zitsman J, Buhler L, Sondermeijer H, McMurchy AN, Levings MK,
Sykes M, Griesemer A.“Restimulation After Cryopreservation and Thawing Preserves the
Phenotype and Function of Expanded Baboon Regulatory T Cells”. Transplantation Direct.
Transplant Direct. 2015 Feb 1;1(1):1-7.
2. Duran-Struuck R, Sondermeijer HP, Bühler L, Alonso-Guallart P, Zitsman J, Kato Y, Wu A,
McMurchy AN, Woodland D, Griesemer A, Martinez M, Boskovic S, Kawai T, Cosimi AB, Yang YG,
Hu Z, Wuu CS, Slate A, Mapara M, Baker S, Tokarz R, D'Agati V, Hammer S, Pereira M, Lipkin WI,
Wekerle T, Levings M, Sykes M. Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on
Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus
Macaques”.Transplantation. 2017 Feb;101(2):274-283
3. Alonso-Guallart P, Zitsman JS, Stern J, Kofman SB, Woodland D, Ho SH, Sondermeijer HP,
Bühler L, Griesemer A, Sykes M, Duran-Struuck R. “Characterization, biology, and expansion
of regulatory T cells in the Cynomolgus macaque for preclinical studies.”Am J Transplant. 2019
Aug;19(8):2186-2198.
3) Development of a Large animal leukemia/lymphoma model: Though mouse models are very
important, in order to improve the predictive value of pre-clinical anti-tumor studies, large animal
models are desperately needed. My research has also focused on the development of a large animal
tumor models of leukemia and lymphoma (K award) to test novel HCT approaches and anti-tumor cell
therapies. There is currently no reliable, clinically-applicable and reproducible large animal cancer
model.
1. Duran-Struuck R, Cho PS, Teague AG, Fishman B, Fishman AS, Hanekamp JS, Moran SG,
Wikiel KJ, Ferguson KK, Lo DP, Duggan M, Arn JS, Billiter B, Horner B, Houser S, Yeap BY,
Westmoreland SV, Spitzer TR, McMorrow IM, Sachs DH, Bronson RT, Huang CA. “Myelogenous
leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias”.
Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):243-56. PMCID: PMC2879595
2. Duran-Struuck R, Matar AJ, Huang CA. “Myeloid Leukemias and Virally Induced Lymphomas
in Miniature Inbred Swine: Development of a Large Animal Tumor Model”. Front Genet. 2015
Nov 20;6:332. doi: 10.3389/fgene.2015.00332. (INVITED)
3. Schenk M, Matar AJ, Hanekamp I, Hawley RJ, Huang CA, Duran-Struuck R. Development of a
Transplantable GFP+ B-Cell Lymphoma Tumor Cell Line From MHC-Defined Miniature Swine:
Potential for a Large Animal Tumor Model. Front Oncol. 2019 Apr 2;9:209. doi:
10.3389/fonc.2019.00209. eCollection 20194. Duran-Struuck R, Huang CA, Matar AJ. “Cellular Therapies for the Treatment of Hematological
Malignancies; Swine Are an Ideal Preclinical Model.”Front Oncol. 2019 Jun 21;9:418. doi:
10.3389/fonc.2019.00418. eCollection 2019. Review. (INVITED)
4) Establishment of immunological tolerance to composite tissue, kidney, liver and islet allografts
and xenografts. Trained by Huang, Sachs and Sykes in the potent immunomodulatory effects of
mixed chimerism guided my research as junior faculty at the Massachusetts General Hospital and at
my laboratories first at Columbia University and now at the University of Pennsylvania to collaborative
research (Sachs, Cetrulo, Yamada, Griesemer) aimed to exploit (and refine) HCT and novel cellular
therapies as a platform for therapies to develop immunological tolerance in macaques and miniature
swine.
1. Liang F, Wamala I, Scalea J, Tena A, Cormack T, Pratts S, Duran-Struuck R, Elias N, Hertl M,
Huang CA, Sachs DH. “Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow
transplantation correlate with failure of engraftment”. Xenotransplantation. 2013 Nov;20(6):458-
68. doi: 10.1111/xen.12065. Epub 2013 Oct 29.
2. Leonard DA, Kurtz JM, Mallard C, Albritton A, Duran-Struuck R, Farkash EA, Crepeau R, Matar
A, Horner BM, Randolph MA, Sachs DH, Huang CA, Cetrulo CL Jr.“Vascularized Composite
Allograft Tolerance across MHC Barriers in a Large Animal Model Am J Transplant. 2014
Feb;14(2):343-55.
3. Pathiraja V, Villani V, Tasaki M, Matar AJ, Duran-Struuck R, Yamada R, Moran SG, Clayman
ES, Hanekamp J, Shimizu A, Sachs DH, Huang CA, Yamada K. “Tolerance of Vascularized
Islet-Kidney Transplants in Rhesus Monkeys” Am J Transplant. 2017 Jan;17(1):91-102.
4. Chaudhry S, Kato Y, Weiner J, Alonso-Guallart P, Baker S, Woodland DC 4th, Lefkowitch JH,
Duran-Struuck R, Sondermeijer HP, Zitsman J, Sears ML, Wu A, Karolewski B, Houck PJ,
Martinez M, Kato T, Sykes M, Griesemer AD. “Transient Mixed Chimerism With
Nonmyeloablative Conditioning Does Not Induce Liver Allograft Tolerance in Nonhuman
Primates.” Transplantation. 2020 Apr 6.
5) Refinement of small and large transplant animal models for pre-clinical studies. I have merged
my expertise in transplantation immunology and clinical laboratory animal and comparative medicine to
develop, improve and refine small and large animal models for auto/allo-immune studies. The 2009
paper in JAALAS has been within the top 10 most cited in the journal and used by many institutions to
establish the care of such animals.
1. Duran-Struuck R, Dysko RC. “Principles of bone marrow transplantation (BMT): providing
optimal veterinary and husbandry care to irradiated mice in BMT studies”. J Am Assoc Lab Anim
Sci. 2009 Jan;48(1):11-22.
2. Pathiraja V., Matar A., Crepeau R, Huang C. Duran-Struuck R. "Development of a safe protocol
of leukophoresis for non-human primates and miniature swine under 10kg”. Journal of the
American Association of Laboratory Animal Science (2013).
3. Duran-Struuck R, Huang CA, Orf K, Bronson RT, Sachs DH, Spitzer TR. Miniature Swine as a
Clinically Relevant Model of Graft-Versus-Host Disease. Comp Med. 2015;65(5):429-43.
4. Zitsman JS, Alonso-Guallart P, Ovanez C, Kato Y, Rosen JF, Weiner JI, Duran-Struuck R.
“Distinctive leukocyte subpopulations according to Organ Type in Cynomolgus Macaques”
Comp Med. 2016. 66(4):308-23
6) Development of immunomodulatory reagents in pre-clinical models for clinical use. Based on
my comparative immunology expertise I actively collaborate with biochemists and molecular
immunologists to develop clinically-applicable reagents of interest with the goal to be translated to the
clinic.
1. Wobma HM, Tamargo MA, Goeta S, Brown LM, Duran-Struuck R, Vunjak-Novakovic. “The
influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal
stem cells.”G. Biomaterials. 2018 Jun;167:226-234. doi: 10.1016/j.biomaterials.2018.03.027.
Epub 2018 Mar 15.2. Wang Z, Duran-Struuck R, Crepeau R, Matar A, Hanekamp I, Srinivasan S, Neville DM Jr, Sachs
DH, Huang CA. “Development of a diphtheria toxin based anti-porcine CD3 recombinant
immunotoxin”. Bioconjug Chem. 2011 Oct 19;22(10):2014-20.
3. Hermanrud CE, Pathiraja V, Matar A, Duran-Struuck R, Crepeau RL, Srinivasan S, Sachs DH,
Huang CA Wang Z “Expression and purification of non-N-glycosylated porcine interleukin 3 in
yeast Pichia pastoris” Protein Expr Purif. 2012 Mar;82(1):70-4
4. Peraino JS, Schenk M, Li G, Zhang H, Farkash EA, Sachs DH, Huang CA, Duran-Struuck R,
Wang Z. “Development of a diphtheria toxin-based recombinant porcine IL-2 fusion toxin for
depleting porcine CD25(+) cells”.J Immunol Methods. 2013 Dec 15;398-399:33-43
D. Additional Information: Research Support and/or Scholastic Performance
Current Support
Helmsley Charitable Trust Foundation (Riley) 01/2018-12/2020
Title: “CAR Tregs for the treatment of T1D”
The goal is to design CAR Tregs to protect donor MHC-I expressing islets across MHC barriers in a T1D NHP
model.
Role: Co-I
R44 AI120443 (Keiser PI) 09/2017-09/2021 NIH/NIAID
Title: S-Nitrosothiol-based rinse/aerosol solutions for treatment/prevention of rhinosinusitis (Phase II)
The goal is to assess the effects of NO using GSNO applications in a rabbit model of chronic inflammation.
Role: Co-I, Pre-clinical studies lead
ITMAT (Duran-Struuck) 03/2018-02/2021
Title: Development of a clinically-relevant swine tumor model through genetic modification of porcine
lymphohematopoietic cancers
The goal is to use develop genetic tools manipulating already established swine leukemias and lymphomas to
be able to engraft in MHC characterized miniature swine.
Role: PI
Completed
Tmunity (Duran-Struuck) 12/2018-01/2019
Title: Pilot study for the treatment of GVHD with genetically engineered PDL1 expressing cells in a pre-clinical
large animal model”
The goal is to use PDL1 as an approach to mitigate GVHD using a cellular approach in large animals.
Role: PIOMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)
BIOGRAPHICAL SKETCH
NAME: Rotolo, Antonia
eRA COMMONS USER NAME: ANROTOLO
POSITION TITLE: Postdoctoral Fellow
EDUCATION/TRAINING
DEGREE/ END
INSTITUTION AND LOCATION FIELD OF STUDY
training DATE
University of Turin, School of Medicine, Turin, Italy MBChB (Honors) 06/2008 Medicine & Surgery
University of Turin, School of Medicine, Turin, Italy MD 06/2014 Internal Medicine
Imperial College London, Hammersmith Hospital,
Honorary SpR 02/2013 Hematology
London, UK
Imperial College London, Hammersmith Hospital, Clinical Research
06/2018 Hematology
London, UK Fellow
Imperial College London, London, UK PhD 03/2019 Immunology
Postdoctoral
University of Pennsylvania, Philadelphia, PA Immunology, Immunotherapy
Fellow
A. Personal Statement
I am a physician-scientist, with board certification in Internal Medicine, subspecialty in Hematology, and research
interest in translational immunotherapy. My clinical practice has been in Hematology/Oncology and
Hematopoietic Stem Cell Transplant (HSCT) for blood and solid tumors. My laboratory research is in the field of
invariant Natural Killer T (iNKT) and Chimeric Antigen Receptor (CAR)-engineered adoptive cell therapies (ACT).
My primary research goal has been to exploit the immune regulatory and anti-tumor properties of iNKT cells for
therapeutic purposes. I completed my doctoral studies at Imperial College London, where with clinical staff at
the John Goldman Centre for Cellular Therapies, Hammersmith Hospital, we established a GMP-grade
procedure for clinical manufacturing of iNKT cell therapeutics for use in cancer patients undergoing allogeneic
HSCT. Moreover, I received top-class training in CAR-T immunotherapy and transplant immunology by CAR-T
pioneers John Maher (King’s College, London) and Carl June (University of Pennsylvania), and HSCT leader
John Goldman (Hammersmith Hospital, London) respectively. In light of my medical background, my research
and career goals are very patient-oriented, with the unwavering desire to understand biological mechanisms to
develop effective therapeutic strategies.
In 2019, I joined the lab of Dr. Nicola Mason at the School of Veterinary Medicine at University of Pennsylvania,
with the goal to conduct iNKT and CAR-immunotherapy studies in pet dogs with spontaneous cancers. This
parallel patient population offers the unique opportunity to perform pre-clinical studies that reliably predict
outcomes of cellular immunotherapies in humans. By pre-clinically validating novel allogeneic immunotherapies
in canine cancer patients, we believe that we can accelerate clinical translation to the human clinics, while
simultaneously advancing both canine and human health care.
1. Rotolo A, et.al. Optimised protocol for clinical scale isolation and expansion of invariant NKT cells for
prevention of aGVHD, EBMT 2015, European Society for Blood and Marrow Transplantation annual meeting
2. Rotolo A, Karadimitris A., Transduction and expansion of Cells, GB1803376.1, 2018.
3. Rotolo A, et al. Enhanced anti-lymphoma activity of CAR19-iNKT cells underpinned by dual CD19 and CD1d
targeting. Cancer Cell 2018 Oct 8;34(4):596-610.e11. PMID:30300581.
4. Rotolo A, et al. A comparative approach to evaluate allogeneic CAR-invariant Natural Killer T cells for solid
tumors, Cancer Moonshot Collaborative Meeting, CMCM 2019, PRECINCT 08.B. Positions and Honors
Positions and Employment
2006 - 2008 Hematology Research Assistant, University of Turin, School of Medicine, Turin, Italy
2008 - 2009 Hematology Clinical Research Scholar, University of Turin, School of Medicine, Turin, Italy
2009 - 2012 Internal Medicine and Hematology Resident, University of Turin, School of Medicine, Turin, Italy
2012 - 2013 Honorary Specialist Registrar, Hematology, ICL, Hammersmith Hospital, London, UK
2013 - 2018 Hematology Clinical Research Fellow, Imperial College London (ICL), Hammersmith Hospital,
London, UK
2014 - 2018 Clinical Research Fellow (PhD program, Immunology), ICL, Hammersmith Hospital, London, UK
2018 - 2019 Postdoctoral Fellow, University of Pennsylvania, Center for Cellular Immunotherapies,
Philadelphia, PA
2019 - Present Postdoctoral Fellow, University of Pennsylvania Veterinary Cancer Center, Philadelphia, PA
Other Experience
2009 - 2014 General Practitioner, Ordine dei Medici Chirurghi ed Odontoiatri, Turin, Italy
2014 - 2016 General Practitioner, General Medical Council, London, UK
2015 OutReach Mentoring Program (mentor), Chemistry Department, ICL, London, UK
2016 - 2018 Specialist Physician, General Medical Council, London, UK
2016 - 2018 Teaching assistant (Hematology/Immunology, lecturer)
2015 - Reviewer assignment, Blood
2017 - Reviewer assignment, Leukemia Research
2018 - Reviewer assignment, Hematology
2019 - Teaching assistant (Molecular Medicine, CAMB542)
Professional Memberships
2015 - Member, European Hematology Association (EHA)
2016 - 2019 Member, British Society of Immunology (BSI)
2017 - Member, American Society of Hematology (ASH)
2017 - Member, Society for Immunotherapy of Cancer (SITC)
2018 - Member, International Society of Cell Therapy (ISCT)
2019 Member, American Society of Gene and Cell Therapy (ASGCT)
2019 Member, National Postdoctoral Association (NPA)
Other Affiliations
2019 Member, Upenn Biomedical Postdoctoral Programs (BPP)
2019 Member, Institute for Translational Medicine and Therapeutics (ITMAT)
2019 Member, Upenn Single Cell Biology (SBP)
Honors and Awards
2009 Optime Training Award, Unione Industriale Torino, Italy
2009 Arneodo Award, Academy of Medicine of Turin, Italy
2017 Abstract Achievement Award, ASH
2018 Early Stage Professional Mentoring Program Award, ISCT
2019 Early Stage Professional Mentoring Program Award, ISCT
Invited Lectures
2011 Academy of Medicine of Torino, Italy
2011 Regional Group of Bone Marrow Transplant, Cuneo, Italy
2015 MRC London Institute of Medical Science, London, UK
2015 West London Lymphoma group, London, UK
2016 Bloodwise, London, UK
2020 Charles University of Prague, Czech Republic
2020 School of Medicine of Pilsen, Czech RepublicC. Contribution to Science
1) Clinical development of iNKT cell-based therapies for transplant and cancer patients. One of the
most remarkable achievements in my research activity was the development and optimization of a robust
protocol for generating large scale iNKT cell-based products. With clinical staff at the Jonh Goldman Centre for
Cellular Therapies, Hammersmith Hospital, London, we established a GMP-grade procedure for clinical
manufacturing of iNKT cell therapeutics. The ultimate goal is to conduct clinical trials to investigate the
therapeutic potential of donor-derived iNKT cells in cancer patients treated with allogeneic HSCT, i.e., prevention
of graft-versus-host disease (GVHD) and graft rejection, and enhancement of anti-tumor immunity.
a. Donor TCRVα24 iNKT cells in the prevention of acute-graft-versus host disease in allogeneic haemopoietic stem cell
transplantation, Imperial Confidence in Concept 2014 grant. Grant award: June 2014
b. Rotolo A, Loaiza S, Finn S-A, Bray E, Pello O, Uddin S, Bradshaw A, Apperley JF, Chaidos A, Karadimitris A,
Optimised protocol for clinical scale isolation and expansion of invariant NKT cells for prevention of aGVHD, EBMT
2015, 41st Annual Meeting of the European Society for Blood and Marrow Transplantation, Pages: S118-S119, ISSN:
0268-3369
2) Preclinical development and validation of a novel CAR-iNKT immunotherapy. My PhD research
work, described in my first-authored research paper published in Cancer Cell journal (a), provided significant
insights regarding the use of CD1d-restricted, invariant NKT cells as an optimal platform to enhance the anti-
tumor potential of CAR immunotherapy. We undertook the first detailed and rigorous comparative analysis of
CAR-iNKT cells vs CAR-T cells showing: i. potent anti-tumor activity of CAR-iNKT cells against relapsed/
refractory B lymphoproliferative disorders, including primary mantle cell lymphoma, marginal zone lymphoma
and chronic lymphocytic leukemia (CLL) cells, where clinical outcomes of conventional autologous CAR-T
therapy remain disappointing; ii. the inherent dual-specificity of CAR-iNKT, as they can dual target tumor cells
expressing both the CAR target, e.g. CD19, and CD1d+, which is recognized by their endogenous invariant TCR;
iii. the remarkable ability of CAR-iNKT cells to eradicate solid-like, brain lymphomas and recurrent disease in
mouse xenografts after just a single dose of CAR-iNKT cells, with no administration of adjuvant cytokines. Given
that less than half of patients with lymphoma/CLL achieve sustained remissions after autologous CAR-T
immunotherapy, this work provided a real prospect for more effective immunotherapy strategies entailing
combination of iNKT platforms with CAR technology.
a. Rotolo A, Caputo V, Holubova M, Baxan N, Dubois O, Chaudhry MS, Xiao X, Goudevenou K, Pitcher D, Petevi K,
Kachramanoglou C, Iles S, Naresh K, Maher J and Karadimitris A. Enhanced anti-lymphoma activity of CAR19-iNKT
cells underpinned by dual CD19 and CD1d targeting. Cancer Cell. 2018 Oct 8;34(4):596-610.e11. doi:
10.1016/j.ccell.2018.08.017. PubMed PMID: 30300581; PubMed Central PMCID: PMC6179961.
b. Rotolo A, Dubois O, Nicoleta Baxan N, Chaudhry S, Caputo V, Goudevenou K, Petevi K, Cheung,Gordon ,i, Gordon
W Cheung, MartinW, Pule M, Maher J, Karadimitris A. Invariant NKT Are a More Effective and Versatile Platform Than
T Cells for CAR Immunotherapy of CD1d-Expressing B Lineage Malignancies: Cellular and Molecular
Mechanisms. AHS Achievement Abstract Award, Blood 2017, December; 130 (Supplement 1): 4613. (Suppl_1.
4613. 4613 ). doi: org/10.1182/blood.V130.
c. Rotolo A, Karadimitris A., Transduction and expansion of cells, Patent application number 1803376.1, 2018, March.
d. Rotolo A, Chaidos A, Karadimitris A. The role of invariant NKT cells in Immunity, The Encyclopedia of
Immunobiology, edited by Michael J.H. Ratcliffe, Elsevier, May 2016, ISBN: 978-0-08-092152-5.
3) Development of a novel canine model for in vivo validation of iNKT-based immunotherapies. The
Mason lab has developed a robust translational research program focused on treating immunologically intact
canine cancer patients as a means to advance both canine and human health care. Most recently, Dr. Mason
has pioneered investigation of CAR therapies and initiated the first CAR-T trial in client-owned dogs with
spontaneous B Non-Hodgkin lymphoma, that will inform implementation of the next generation CAR-T therapies
for human trials. Under her mentorship, I have found that canine iNKT are phenotypically and functionally similar
to human iNKT and can be isolated, gene engineered and/or expanded up to clinical scale using the same
protocols as human iNKT cells. This suggests that immunocompetent pet dogs with spontaneous cancer can be
used as a clinically relevant ‘model’ to pre-clinically validate iNKT-based immunotherapies and strongly support
the feasibility of pre-clinical trials in canine patients using in vitro expanded canine iNKT cell products.
a. Rotolo A, et al. A comparative approach to evaluate allogeneic CAR-invariant Natural Killer T cells for solid tumors,
Cancer Moonshot Collaborative Meeting, CMCM 2019, PRECINCT 08.4) Elucidation of molecular pathogenetic mechanisms of blood cancers for identification of novel
therapeutic targets. Since my undergraduate studies, a significant part of my research work has been focused
on unravelling novel pathogenetic mechanisms of blood cancers for the purposes of targeted therapies (a). In
the Karadimitris lab (Imperial College London), I contributed to studies aiming to elucidate the role and molecular
determinants of transcriptional and epigenetic deregulation in multiple myeloma (b, c). Our in vitro molecular
dissection and in vivo studies identified BET proteins as regulators of oncogenic Myc transcription in multiple
myeloma and demonstrated the therapeutic impact of the BET protein inhibitors I-BET-151 and -762 on pre-
clinical myeloma (b). As a result, in collaboration with other major institutions in the UK and USA and supported
by GSK, we participated in a phase I clinical trial aiming to define the safety and efficacy of I-BET-762 in
hematological malignancies.
a. Messa E, Carturan S, Maffè C, Pautasso M, Bracco E, Roetto A, Messa F, Arruga F, Defilippi I, Rosso V, Zanone C,
Rotolo A, et al. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting
independently from cell iron deprivation by chelation and reactive oxygen species scavenging. Haematologica.
2010;95(8):1308-16. PMCID: PMC2913079
b. Chaidos A, Caputo V, Gouvedenou K, Liu B, Marigo I, Chaudhry MS, Rotolo A, Tough DF, Smithers NN, Bassil AK,
Chapman TD, Harker NR, Barbash O, Tummino P, Al-Mahdi N, Haynes AC, Cutler L, Le B, Rahemtulla A, Roberts I,
Kleijnen M, Witherington JJ, Parr NJ, Prinjha RK, Karadimitris A. Potent antimyeloma activity of the novel bromodomain
inhibitors I-BET151 and I-BET762. Blood 2014;123(5):697-705. PubMed PMID: 24335499.
c. Caputo V, Goudevenou K, Trasanidis N, Petevi K, Xiao X, Ponnusamy K, Iskander D, Pitcher D, Rotolo A, Auner
HW, Chaidos A, Karadimitris A. Myeloma Cell Addiction to the Transcription Factor TCF11, 59th Annual Meeting of
the American-Society-of-Hematology, ASH, 2017, ISSN: 0006-4971
5) Clinical investigation of novel targeted and stem cell-based therapeutics in hematological
malignancies. While serving as a Hemato-Oncology physician and BMT specialist at San Luigi Hospital,
University of Turin (Italy), and Hammersmith Hospital, Imperial College London (UK), I was co-investigator in
clinical trials testing new therapeutic strategies in cancer and transplant patients. The results of such studies had
great positive impact on our clinical practice and prompted implementation of procedures and infusion strategies
to further improve clinical outcomes in these patients.
a. Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R,
Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D,
Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G,
Vannucchi AM, Barbui T; CYTO-PV Collaborative Group, Barbui T, Finazzi G, Marchioli R, Specchia G, Masciulli A,
Marfisi RM, Cavazzina R, Scarano M, D'Amico A, Ferri B, Guido C, Marfisi L, Pera C, Polidoro A, Marchioli R, Sacco
M, Levantesi G, Tognoni G, Barosi G, Carobbio A, Leoni P, Scortechini AR, Mulattieri S, Tomassetti S, Honorati E,
Specchia G, Ricco A, Albano F, Pastore D, Carluccio P, Mazzone AM, Rossi AR, Finazzi G, Finazzi MC, Delaini F,
Falanga A, Rambaldi A, Quarta G, Guaragna G, Giannotta A, Angelucci E, Usala E, Simula MP, Pilo F, Cacciola R,
Cacciola E, Pezzella F, Seria E, Di Francesco E, Rapezzi D, Gallamini A, Bertolotti L, Vannucchi AM, Antonioli E,
Guglielmelli P, Pieri L, Susini MC, Bartalucci N, Bosi A, Musolino C, D'Angelo A, Centorrino R, Gerace D, Allegra A,
Iurlo A, Cortelezzi A, De Philippis C, Ferretti E, Ciceri F, Claudiani S, Lunghi F, Malato S, Trinca S, Pogliani EM, Belotti
A, Lanzi E, Elli EM, Gaidano G, Lunghi M, Deambrogi C, Rossi D, Saglio G, Cilloni D, Rotolo A, Zanone C, Randi ML,
Bertozzi I, Tezza F, Aneloni V, Siragusa S, Quintini G, Saccullo G, Caracciolo C, Cazzola M, Casetti I, Elena C, Landini
B, Rumi E, Visani G, Barulli S, Guiducci B, Lucesole M, Malerba L, Isidori A, Santini S, Grossi A, De Stefanis M, Biagioni
C, Tieghi A, Merli F, Imovilli A, Codeluppi K, Rubagotti S, Romano N, Bonini A, Bellesia E, Musto P, Martorelli MC,
Villani O, Zifarone E, Zonno A, Santopietro V, De Stefano V, Za T, Rossi E, Ciminello AM, Betti S, Alimena G, Latagliata
R, Tafuri A, Breccia M, Carmosino I, Spadea A, Pisani F, Romano A, D'Andrea M, Cascavilla N, Nobile M, Mantuano
FS, Rossi G, Tricarico M, Rodeghiero F, Ruggeri M, Bedin F, Lissandrini L, Finotto S.. "Cardiovascular events and
intensity of treatment in polycythemia vera." N Engl J Med 2013; 368(1): 22-33.
b. Rotolo A, Pavlu J, Davidson H, Lasa M, Palanicawandar R, Giles C, MacDonald D, Marin D, Milojkovic D, Rahemtulla
A, Apperley J, Kanfer E, 2013, LACE reduced intensity conditioning for high-risk haematological malignancies: a 22-
year single-centre experience, 39th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation
EBMT 2013, Pages: S235-S235, ISSN: 0268-3369
c. Sevillano B, Pavlu J, Szydlo R, Rotolo A, Khoder A, Sever M, Lasa M, Palinacawandar R, Giles C, Chaidos A,
MacDonald D, Karadimitris A, Gabriel I, Marks A, Milojkovik D, Olavarria E, Rahemtulla A, Apperley J, Kanfer E. LACE-
conditioned allogeneic transplantation for high-risk haematological malignancies: treatment outcomes in 62 patients
from a single centre. EBMT 2015; Istanbul. NATURE PUBLISHING GROUP; c2015.
Complete List of Published Work in MyBibliography:
https://www.ncbi.nlm.nih.gov/myncbi/1bMnqI6zeTvQb5/bibliography/public/Program Director/Principal Investigator (Aronson, Lillian, R.)
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME POSITION TITLE
Lillian Ruth Aronson VMD, DACVS Professor of Surgery
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY
(if applicable)
Lehigh University, Bethlehem, PA BS 1988-1992 Biology
University of Pennsylvania, School of Veterinary
VMD 1992-1993 Veterinary Medicine
Medicine
University of Pennsylvania, School of Veterinary
Internship 1992-1993 Veterinary Medicine
Medicine
University of California, Davis, School of
Residency 1993-1996 Veterinary Surgery
Veterinary Medicine
University of California, Davis, School of
Lecturer 1996-1997 Veterinary Surgery
Veterinary Medicine
A. Personal Statement
I am a veterinarian with board certification in veterinary surgery. During my residency and
lectureship at UC Davis, I trained under Dr. Clare Gregory learning and honing my skills in
microvascular surgery and renal transplantation. I was recruited to the University of
Pennsylvania as a Lecturer in 1997 when I initiated the School’s renal transplant program. Since
this time, I have performed approximately 170 feline renal transplants and 3 canine renal
transplants. The program is acknowledged as the top program in the United States and draws
its caseload from across the entire country and abroad. Unlike the procedure in cats, renal
transplant in dogs is significantly hindered by a lack of suitable matched donors and an
unacceptable high complication rate associated with the intense immune suppression required
to prevent graft rejection. The goal of this fellowship project is very exciting and if successful,
would revolutionize our ability to perform successful organ transplantation in dogs. As a faculty
member in the Surgery section, I have successfully mentored 64 surgical residents and I am
very excited to contribute to advancing the career of a translational veterinary scientist in the
field of transplantation immunology and adoptive T cell therapies.
B. Positions and Honors
Positions and Employment
1994-1997 Coordinator of the renal transplant program at the UC Davis Veterinary School
1997-2000 Senior Research Investigator, University of Pennsylvania Veterinary School
2000-2006 Assistant Professor of Surgery
2006-2012 Associate Professor of Surgery
2012-present Professor of Surgery
1997-present Founder and coordinator of the renal transplant program at the University of
Pennsylvania, School of Veterinary Medicine
C. Contribution to Science
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