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2021
Paths of
Progress
Research and Care
at Dana-Farber
Cancer Institute
The Cellular
Therapies
Revolution:
Dana-Farber
Scientists
Power Ongoing
Innovation
PLUS:
The Rise in Young Onset Colorectal Cancer
Researchers Pivot to Battle COVID
Dana-Farber’s 2020 Annual Report
TABLE OF CONTENTS
2021 Volume 28, Number 1
12
6 18
FEATURES DEPARTMENTS
6 Cancer Scientists Pivot to Battle COVID-19 2 Around the Institute
Dana-Farber researchers deployed their cancer News and highlights from Dana-Farber
expertise and ingenuity in the global fight against
32 CAR T-Cell Therapy Changes Landscape
the COVID-19 pandemic.
How one patient is being helped by a newly FDA-
12 Youth Is Served approved treatment for mantle cell lymphoma.
The Young-Onset Center is building a new model
33 Drawing on Strength in the Face of Uncertainty
of care for the nation’s growing population
A young woman uses positivity and perseverance in
of young adults diagnosed with colorectal cancer.
the face of a stage IV lung cancer diagnosis.
18 The Cellular Therapies Revolution
Dana-Farber scientists drive ongoing innovations 34 Dana-Farber 2020 Annual Report
in cell therapies designed to improve the
immune system’s ability to fight cancer.
26 Eliminating Cancer’s Building Blocks
How researchers are working to pioneer a new class
of cancer drugs designed to make tumor-promoting
proteins disappear.
Vi si t Da n a - Fa r b e r o n lin e . www.d a n a -f a rb e r. o rg
Paths of Progress is published by Dana-Farber Cancer Institute.
Copyright © 2021 Dana-Farber Cancer Institute. All rights reserved.
PRESIDENT’S LETTER
DEAR READERS
At Dana-Farber, we measure the impact of our work by the
response our patients have to treatment: Is a patient helped by a
particular therapy and to what extent? Are the side effects manage-
able? How can the response be improved?
As an institution dedicated to advancing the fight against cancer,
we are judged, ultimately, by how well we respond – to unexpected
challenges, to scientific opportunities, and to broad-scale changes
affecting our society. Events of the past year have tested us in ways
few of us could have predicted – and demonstrated how agile and
creative an organization we can be.
This issue of Paths of Progress can be read as a sampler of how
Dana-Farber has met the moment. One article examines how Insti-
tute scientists have brought their knowledge of cancer and cancer
treatment to devise treatment strategies for COVID-19. Another
focuses on the Young-Onset Colorectal Cancer Center, a clinical and
research hub established to confront an alarming rise in colorectal
“As an institution dedicated to
cancer rates in people under age 50.
advancing the fight against cancer,
Our cover story on the ongoing revolution in cellular therapies
we are judged, ultimately, by how
illustrates the rapidity with which the cancer field in general, and
well we respond – to unexpected
Dana-Farber in particular, have seized on the promise of these
challenges, to scientific opportunities,
treatments, which are made by modifying immune system cells
and to broad-scale changes affecting
so they can better identify and kill cancer cells. The final story
our society.”
recounts how a Dana-Farber discovery of the mode of action of
the drug lenalidomide inspired researchers to develop an entirely
– Laurie H. Glimcher, MD
new type of cancer agent, one that, instead of merely disabling
cancer-related proteins, uses the cell’s natural disposal machinery
to eliminate them.
Just as cancer is often treated most effectively when it’s caught
in its earliest stages, institutions that are quickest to identify
research opportunities and develop them into treatments have a
decided edge. That has always been a priority at Dana-Farber. It’s
not just a matter of responsiveness; we see it as our responsibility.
Laurie H. Glimcher, MD
President and CEO, Dana-Farber Cancer Institute
AROUND THE INSTITUTE New Benderson Family Program for Triple-Negative Breast Cancer Dana-Farber in 2020 received a $5 million gift from “It will also allow us to fund crosscutting initiatives the Benderson Family of Sarasota, Florida, that will at Dana-Farber that will make a difference in the way accelerate research in triple-negative breast cancer cancer is treated and benefit all patients here.” (TNBC) and strengthen the Institute’s capabilities for Triple-negative breast cancer is one of the most treating this disease. The gift establishes the Bender- challenging forms of breast cancer to treat. Despite son Family Program for Triple-Negative Breast Cancer recent advances forged by physician-scientists at and represents the largest philanthropic donation to Dana-Farber and elsewhere, new and novel treatment TNBC research at Dana-Farber. approaches for TNBC patients are needed. Currently, The commitment by the Benderson Family provides chemotherapy remains the backbone of treatment for the resources for Dana-Farber to expand a novel TNBC, but with the ongoing research at Dana-Farber, comprehensive TNBC research registry and establish supported by the Bendersons, new therapies including a new endowed fund, the Benderson Family Endow- immunotherapies, antibody drug conjugates, and PARP ment for Triple-Negative Breast Cancer Research. The inhibitors are being tested for the treatment of this resulting robust TNBC cohort will provide the data type of cancer. and samples necessary to conduct vital laboratory TNBC describes breast cancer cells that do not experiments, identify potential drug targets, and de- have estrogen, progesterone, or HER2 receptors. sign clinical trials for the more effective treatment and TNBC makes up approximately 10-15% of all breast improved outcomes for TNBC patients. Additionally, cancers and is usually more aggressive than estrogen the gift will support capital projects and strategic ini- receptor-positive breast cancer and HER2-positive tiatives under the leadership of Dana-Farber President breast cancer. This disease is often found in younger and CEO Laurie H. Glimcher, MD. women (under age 40) and in women of African Ameri- “The Bendersons’ generous gift will allow Dr. Eric can or Hispanic background. The disease may also be P. Winer and Dana-Farber to continue to lead the way associated with having an inherited mutation in the in TNBC research and patient care,” said Glimcher. BRCA1 gene. Dana-Farber’s Chestnut Hill Location Now Open In late January 2021, Dana-Farber cancer and provide our special gists, radiation oncologists and completed its latest expansion of model of care in this new Chestnut others will provide quality multidis- oncology services in the Boston Hill location,” said Laurie H. Glimcher, ciplinary care. metro area with the opening of MD, president and CEO, Dana-Farber a new hospital facility to provide Cancer Institute. “The facility incor- increased outpatient care and porates feedback from patients and services. The 140,000-square-foot families with many details throughout Dana-Farber Cancer Institute – to ensure convenience and comfort.” Chestnut Hill facility is on the top Dana-Farber provides adult two floors of the Life Time Center clinical care in collaboration with (formerly the Atrium Mall) at 300 Brigham and Women’s Hospital as Boylston Street in the Chestnut Hill Dana-Farber/Brigham and Women’s area of Newton, Mass. Cancer Center (DF/BWCC). At the “We are thrilled to expand our new facility, Brigham and Women’s ability to serve more people with Hospital oncology surgeons, radiolo- Dana-Farber Chestnut Hill 2 Paths of Progress 2021 Dana-Farber Cancer Institu te
AROUND THE INSTITUTE
Ebert Awarded Sjöberg Prize for Cancer Research
Dana-Farber’s Benjamin Ebert, cancer growth have proven difficult cancer diagnosis.
MD, PhD, chair of Medical Oncol- to target using pharmaceuticals. Dr. Ebert is an Investigator of the
ogy, was in 2021 awarded the Sjö- Ebert’s discovery shows that it may Howard Hughes Medical Institute,
berg Prize, an annual international be possible to direct such proteins elected member of the National
prize in cancer research. It was so that they are degraded and thus Academy of Medicine, the Ameri-
awarded for Ebert’s discovery of stop the growth of the tumor.” can Society for Clinical Inves-
the mode of action of lenalidomide This is the fifth time that the tigation, and the Association of
in the treatment of hematologi- Sjöberg Prize will be awarded. The American Physicians. He served as
cal disorders. Bengt Westermark, Royal Swedish Academy of Scienc- president of the American Soci-
chair of the prize committee, noted es selects the laureates and the Sjö- ety for Clinical Investigation. His
Ebert’s discovery as “epoch- berg Foundation provides the financ- additional awards include the Till
making” and believes that it will be ing. The prize amounts to $1 million, and McCollough Award from the
extremely important in the devel- of which $100,000 is the prize sum International Society of Experi-
opment of new cancer drugs. and $900,000 is funding for future mental Hematopoiesis, the William
“So far, the greatest clinical ben- research. The prize was established Dameshek Prize from the American
efit is in the treatment of multiple by businessman Bengt Sjöberg to Society of Hematology, the Mey-
myeloma, which is a bone mar- promote scientific research with a enburg Prize, and mentoring and
row disease,” said Westermark. primary focus on cancer, health, and teaching awards from Harvard
“Many of the proteins that drive the environment, following his own Medical School.
Expert Recommendations on Cancer Inequities
New recommendations co-developed by Dana- focus on health equality, prioritizing efforts with the
Farber call for a significant expansion of the National greatest potential impact; understand and address
Cancer Institute (NCI) and its Comprehensive Cancer structural barriers to equitable cancer outcomes;
Centers to understand the causes of inequities in improve access to quality care by collaborating with
cancer care and a commitment to building sustained community partners; advance legislation and poli-
partnerships to reduce them. Published in the March cies that support cancer control; and evaluate the
2021 issue of Health Equity, the recommendations are effectiveness of community outreach programs and
based on a 2019 listening session with the NCI and implement improvements as needed.
the broader cancer community on efforts to address “We need to find ways to
disparities in cancer care. better align our research
“Events of the past year have brought renewed at- with the community’s needs
tention to issues of health equity – how we think about – to build relationships that
the ways that structural racism, income disparities, have durable results for
and geographic location, affect the care that people people in the community,”
receive,” said Christopher Lathan, MD, MS, MPH, Lathan remarked. The rec-
faculty director for cancer care equity at Dana-Farber, ommendations set forth pro-
senior author of the work. vide an agenda for efforts
The 2019 meeting identified five major opportunities going forward, says Lathan.
for the NCI and cancer centers to improve the impact Learn more in Health Equity Christopher Lathan, MD,
of community outreach, including: adopt an explicit at http://liebertpub.com/heq. MS, MPH
www.dana-farber.org 3
AROUND THE INSTITUTE
Dana-Farber Announces Historic Fundraising Campaign
Dana-Farber announced in May 2021 that it has “Achieving the ambitious goals of
embarked on the most ambitious fundraising
campaign in its history. The Dana-Farber Campaign The Dana-Farber Campaign will
aims to raise $2 billion to advance the Institute’s
mission and defy cancer by accelerating its work take the deep engagement of
through revolutionary science, extraordinary care,
and exceptional expertise. our full community of supporters.”
“We know more about cancer than ever before,”
said Laurie H. Glimcher, MD, president and CEO, – Michael Eisenson
Dana-Farber. “We are relentlessly determined to
take what we are learning, build on it, and defeat this
disease. The Dana-Farber Campaign will provide areas including cancer prevention and early
the resources to allow us to prevent, beat, and defy detection, drug development, epigenetics, genomics,
cancer, resulting in more lives saved, and more immunotherapy, pediatric cancers, and data science,
dreams realized.” including artificial intelligence and machine learn-
The Dana-Farber Campaign is the largest campaign ing. Campaign support will also spark innovations in
in New England history focused entirely on cancer. research-based care and allow Dana-Farber to
It comes at a crucial time, when scientific progress expand access to the extraordinary care it is known
is at an all-time high, yet the need for innovations in for, reaching even more patients and families by
research and care is still great. Discoveries and bringing high-quality cancer care to underserved
treatment options are increasing at an extraordinary populations, as well as through expanded telemedi-
pace for many cancers, but other cancers remain cine and additional locations.
difficult to diagnose early and hard to treat. Certain Funding will enable Dana-Farber to attract
cancers are now striking younger people more new talent and support its world-class clinicians
frequently, and many barriers to equitable cancer and scientists through endowed donor-named
care still exist. The Dana-Farber Campaign chairs, investigatorships, and fellowships, giving
aims to build on recent successes, overcome long- them more time to spend with patients and
standing challenges, and change the future of expanded opportunities to pursue breakthrough
cancer medicine. research ideas.
Campaign funding will support critical research “Achieving the ambitious goals of The Dana-Farber
Campaign will take
the deep engagement
of our full community
of supporters,” said
Michael Eisenson,
chair of The Dana-
Farber Campaign and
Institute Trustee.
“With that support,
Dana-Farber will lead
the work to defy
cancer, and achieve
what was once
thought impossible.”
4 Paths of Progress 2021 Dana-Farber Cancer Institu te
AROUND THE INSTITUTE
New Lavine Family Fund for Preventative Cancer Therapies
A $25 million gift from Jonathan Lavine, co-managing methods and therapies will enable doctors to save more
partner at Bain Capital, and his wife, Jeannie Lavine, lives,” says Jonathan Lavine. “It is too common that
will establish a dedicated fund for preventative cancer cancer is not discovered and diagnosed until a patient is
therapy research at Dana-Farber and endow three experiencing symptoms, at which point the cancer has
chairs to form the Lavine Family Chairs for Preventative progressed to a point where it is not easily treated. To
Cancer Therapies. This gift will enable Dana-Farber to defeat cancer, early detection and prevention research
invest dedicated research to life-saving preventative are absolutely critical.”
cancer research, helping identify high-risk patients and This is not the first time that the Lavines have made
using preventative cancer therapies to diagnose and a life-changing gift to Dana-Farber. The Lavines were
treat cancer before it starts. personally impacted by cancer when Jonathan Lavine’s
Through the Lavine Family Chairs for Preventative mother was diagnosed with non-Hodgkin lymphoma
Cancer Therapies, three researchers will be able to over two decades ago. Lavine was able to witness the
dedicate resources to investigating precursor condi- work of Dana-Farber firsthand as his mother received
tions, immunotherapies, and other potential preven- successful treatment, and was inspired to give back
tion therapies. This gift will also help researchers to to Dana-Farber. In 2013, Jeannie and Jonathan Lavine
develop new methods of early detection and enhance gave $10 million to an initiative to enhance the patient
the ability of doctors to identify and test for early- and family experience at Dana-Farber. Jonathan
stage cancers. Lavine says, “The work at Dana-Farber saves lives
“Early detection and cancer prevention are essential and it is our honor to be a small part of making those
to the fight against cancer. Effective early detection miracles happen.”
$30M Gift Establishes the Center for C.A.R.E.
Thanks to an extraordinary $30 million gift from an Rafael Irizarry, PhD, chair of the Department of Data
anonymous donor, Dana-Farber in 2020 created the Science, to enable recruitment, training, and sup-
Center for C.A.R.E. (Cancer Analytics & Research port for the next generation of data science experts.
Exploration), which supports the important work of • $5 million established an endowed fund, the En-
the Institute’s Department of Data Science to improve dowment for the Knowledge Systems Group, under
patient outcomes through data-driven approaches, the direction of Ethan Cerami, PhD, director of the
better understand the biology of cancer, test the Knowledge Systems Group, to provide funding in
efficacy of treatments, and extract actionable knowl- perpetuity for innovative projects and sophisticated
edge from complex datasets. This transformative gift, platforms that point clinicians and their patients to
the largest to data science in Dana-Farber’s history, treatments offering the best possible outcomes.
will be allocated to three key areas:
The anonymous donor was inspired to establish
• $20 million supports state-of-the-art lab space the Center for C.A.R.E. in the hopes of helping pa-
to dramatically increase collaborative opportuni- tients live longer and better lives. “I know what
ties for data scientists and accelerate solutions to it is to lose someone to cancer and feel helpless
complex problems. and overwhelmed,” said the donor. “That is why
• $5 million established a current-use fund, the I wanted to make this gift so that people every-
Fund for Junior Data Science Research Investigators where can get the right intervention to treat their
and Post-Doctoral Fellows, under the direction of specific cancer.”
www.dana-farber.org 5
Cancer Scientists Pivot
to Battle COVID-19
Deploying Dana-Farber expertise
against a global pandemic
BY RICHARD SALTUS
I
n early 2020, as the pandemic inflammatory, anti-thrombotic, and
erupted, Dana-Farber physi- pro-fibrinolytic, which reverses
cian-scientist Paul Richardson, endothelial injury. Driven by the
MD, read reports of COVID-19 similarity to the blood vessel com-
patients developing life-threat- plications in COVID-19 patients,
ening blood clots in their lungs he and other experts formed an
and other organs – and he quickly international study group to test
became intrigued. defibrotide as a treatment option
It reminded Richardson of for patients infected with the virus.
another disease he knew Preclinical studies by the group in
extremely well: veno-occlusive allogenic transplant mouse models
disease (VOD), a serious throm- performed at Johns Hopkins and
botic complication of bone in Spain showed 80% survivorship
marrow transplants that blocks for animals with severe lung injury
circulation in the liver and is treated with defibrotide, compared
underpinned by endothelial dam- to zero in the control group, and
age triggered by the effects of these results further strengthened
both chemotherapy and inflam- the rationale for clinical trials in
mation of the transplant itself. COVID-19.
Richardson, director of Clinical Early reports from clinical tri-
Research for the Jerome Lip- als showed “some remarkable
per Multiple Myeloma Center at results,” says Richardson, even
Dana-Farber, has pioneered the when patients receiving defib-
treatment of VOD with defibrotide, rotide had been devastatingly ill
a naturally derived first-in-class on ventilators and were worsening
Paul Richardson, MD compound which has proved anti- despite receiving other treatments.
6 Paths of Progress 2021 Dana-Farber Cancer Institute
In February 2020, a trial of defi- “Many investigators, both lab and clinical,
brotide led by Richardson and col-
leagues opened at Brigham and followed their own interests on aspects of
Women’s Hospital, with other cen-
ters in Boston and New England. COVID-19.”
This was in addition to an ongoing
study in Michigan. Initial results – William Hahn, MD, PhD
have been especially encourag-
ing, also with complete responses permission to stay operational, Center for Advanced Molecu-
and recovery in 80% of critically ill though with a skeleton crew,” lar Diagnostics at Brigham and
patients treated so far, with excel- says Kevin Haigis, PhD, Dana- Women’s, says Bruce Johnson,
lent safety to date. Farber’s chief scientific officer. MD, chief clinical research officer
“Much of what we know about “Many investigators, both at Dana-Farber.
cancer can also help in the fight lab and clinical, followed their
against COVID-19,” says Laurie own interests on aspects of A Race for COVID-19 Drugs
H. Glimcher, MD, president and COVID-19,” adds William Hahn, and Antibodies
CEO of Dana-Farber. “Dana- MD, PhD, chief operating officer While clinical investigators like
Farber scientists are using their at Dana-Farber. “We wanted Richardson followed leads on
cancer knowledge to develop to help those who had meritor- how the COVID-19 virus affected
potential treatments for the ious projects to be able work patients, Dana-Farber laboratory
novel coronavirus.” during the early phases of the scientists focused on clues in the
While most Dana-Farber labo- pandemic when the labs were basic genetic information that en-
ratories were shut down early in mostly closed.” ables the coronavirus to replicate
the second quarter of 2020, “labs In addition, the Center for and infect human cells. In early
working on COVID, or wanting to Cancer Genomics helped develop 2020, scientists in China decoded
work on COVID, could request different COVID-19 tests for the and shared the genetic sequence
www.dana-farber.org 7
– the instruction manual – of and we know how its proteins op-
SARS-CoV-2, the COVID-19 virus, erate, so we know where to target”
touching off a race in labs around parts of the virus with compounds
the world to develop potential that could lead to drug treatments,
treatments. says Haribabu Arthanari, PhD, a
Thanks to the genetic sequence cancer biologist at Dana-Farber.
and the subsequent high-resolu- However, finding chemical com-
tion structures that were pub- pounds that closely and exclusively
lished, coupled with the similarity match and bind to key parts of
of SARS-CoV-2 to other coronavi- the virus – which is essential to
ruses, “We know exactly what the creating a drug – is a massive and
components of this virus look like time-consuming process.
New Strategies Keep Research on Track
The COVID pandemic forced getting medications at home by mail gradually in the first half of 2020,
sweeping changes to Dana-Farber or having laboratory tests done at with strict limits on how many
laboratory and clinical research outside facilities, and patient safety people could occupy a laboratory
routines in early 2020 to pro- wasn’t compromised. workspace, meaning that some
tect the safety of scientists and By early 2021, said Tolaney, clini- groups worked in shifts, and
patients. Some experiments were cal research in most ways returned group meetings were prohibited.
halted or put on hold; most labora- to normal, with some exceptions. But since last June, “my lab has
tory investigators vacated their “All our therapeutic trials have been back to work full-time,”
workspaces and group meetings reopened so we can do all our says James DeCaprio, MD, chief
were curtailed; telemedicine inter- normal research activities,” said of the Division of Molecular and
actions replaced in-person visits Tolaney, who is the director of the Cellular Oncology at Dana-Farber.
for many patients; and experimen- breast oncology clinical trials pro- “My lab has enough bays to
tal drugs were shipped to patients gram and associate director of the accommodate everyone, but a
rather than being dispensed at Susan F. Smith Center for Women’s few labs still have to do shift work
the Institute. Cancers. “Some things have because they have more people
In the clinical trials arena, continued, such as telehealth visits than bays.”
restrictions limited enrollment and shipment of oral investigational Principal investigators can
of some patients and slowed therapies, which I think has been spend up to days a week in their
the launching of new trials. One wonderful for patients.” labs , but since in-person meet-
significant limitation was that re- Social distancing requirements ings are strictly limited, “there is
searchers accustomed to analyz- still in effect have meant many little reason for me or any other PI
ing fresh biopsy tissues from the research coordinators work from to go to the lab,” DeCaprio says.
operating room had to make do home or rotate through the main “Zoom has replaced these meet-
with frozen specimens. However, campus. In fact, says Tolaney, the ings and works pretty well for the
a study published in 2020 led by experience has been beneficial in most part,” he adds. “Certainly,
Sara Tolaney, MD, MPH, found some ways: “We’ve learned a lot Zoom has enabled a lot of col-
that in large part workarounds of lessons about things that can be laborations with other institutions
enabled most participants to stay done remotely.” across Boston, the United States,
on clinical trials, even if it meant Research laboratories re-opened and the rest of the world.”
8 Paths of Progress 2021 Dana-Farber Cancer Institu teArthanari is working with “We know exactly what the components of this
postdoctoral fellow Christoph
Gorgulla, PhD, who developed a virus look like and we know how its proteins
super-fast computational drug-
screening platform. Using this operate, so we know where to target.”
platform, Arthanari and Gorgulla
screened more than one billion – Haribabu Arthanari, PhD
compounds each against 40
different sites on 17 different
proteins – 15 of which belong to virus proteins are existing drugs, and thereby foil virus infection.
the SARS-CoV-2 virus and two of including 161 that have been ap- The work is funded through a
which belong to human pro- proved for human use. Arthanari Dana-Farber collaboration with
teins – which enable the virus to says that 16 of these drugs are Takeda Pharmaceutical Co.
bind to (and infect) human cells. being considered for clinical trials Patients infected with coronavi-
The screening process gener- in COVID-19 patients. This work rus attempt to fight it off with anti-
ated more than 1,000 “hits” — was recently published in the bodies generated by the immune
matches, for each of the 40 sites journal Science and all the data system. These natural antibodies
that were targeted, that poten- is made freely available to the – proteins with a highly specific
tially could enable compounds research community. affinity for parts of the virus – can
to dock or bind to sites on the “Many of the sites we screened be isolated from people who have
protein molecules. This extremely were not yet targeted by other recovered from COVID-19 and
high-throughput screening was groups, but the initial results are their plasma antibodies can be
accomplished in four weeks using very promising,” says Arthanari. used to treat patients with severe
computer resources from Google “Thus, we explore new avenues COVID-19. These antibodies can
Cloud, resulting in more than 50 on how to tackle the virus.” also be isolated from immune
billion docking instances. Carl Novina, MD, PhD, studies cells from recovered individuals
Some of the compounds that the biology of RNA, the infor- or from large human antibody
matched sites on the COVID mation molecule in the COVID libraries and then used to manu-
virus. He and facture huge quantities of mono-
his colleagues clonal (identical) antibodies in the
developed a laboratory. Monoclonal antibodies
system to rapidly can then become the basis of
screen for drugs vaccines and drug treatments.
that disrupt the Wayne Marasco, MD, PhD, an
interactions be- expert in creating monoclonal
tween RNAs and antibodies, is leading a COVID-19
the proteins that Protective Immunity Study. The
bind to them. study has enrolled 150 volunteers,
The goal of this including health care workers,
work is to screen cancer patients, and others, who
for drugs that recovered from COVID-19 infec-
disrupt RNA- tion. Their blood will be analyzed
protein interac- to look for antibodies that have
Irene Ghobrial, MD, heads the IMPACT study looking at how tions crucial for been generated against the virus,
COVID infections and vaccinations affect people with precur- SARS-CoV-2 to and which could be used in devel-
sor blood cancer conditions. replicate itself oping vaccines and treatments.
www.dana-farber.org 9Adult Leukemia Program, is lead-
ing the PRE-VENT trial.
Cancer Patients and
Coronavirus Vaccines
Dana-Farber scientists are also
focusing on a major concern at
the Institute: the increased vulner-
son’s work with defibrotide is one ability of cancer patients to the
example. Another trial, headed by coronavirus. Studies have shown
Steven Treon, MD, PhD, is exam- cancer patients to be at signifi-
Haribabu Arthanari, PhD, is using a new
ining the use of ibrutinib, a drug cantly higher risk of infection and
rapid screening platform to look for used in treating blood cancers, of developing severe disease.
compounds to attack the COVID virus. to prevent lung injury in patients One reason is that their immune
infected with the coronavirus. systems are frequently weakened
Francisco Marty, MD, who was by the disease or the therapies
Antibodies produced by the an infectious disease specialist at used to treat it, leaving them more
immune system that block the Dana-Farber, led trials at Brigham susceptible to infection.
activity of an infectious agent are and Women’s Hospital of the However, there is still a lot to
called neutralizing antibodies. antiviral drug remdesivir, which be learned about the interaction
However, they are not always is the only approved drug to treat of COVID and cancer, and many
totally effective in preventing COVID-19. He also led a clinical questions are unanswered. Among
disease. Joseph Sodroski, MD, a trial of a “cocktail” of different them: which cancer patients are at
Dana-Farber researcher who has monoclonal antibodies made by highest risk of severe COVID-19 in-
studied the AIDS virus for many Regeneron to treat hospitalized fection? How does immunotherapy
years, participated in a published patients with COVID-19. or treatment that suppresses the
study that found a diverse set of Another clinical trial, known as immune system influence suscep-
potent neutralizing antibodies in PRE-VENT, is trying to determine tibility to the coronavirus? How do
the blood of severely ill COVID-19 if a drug, pacritinib, a JAK inhibi- chemotherapies and targeted drug
patients. Tests showed that these tor used in treating myelofibrosis therapies influence vulnerability?
neutralizing antibodies could very – a rare form of cancer – can Could cancer immunotherapies
effectively block virus particles prevent acute respiratory distress such as checkpoint inhibitor
from infecting cells. Such antibod- syndrome in patients with severe drugs help? When is it safe to
ies “could be used to lessen the COVID-19 disease. JAK inhibitors resume cancer therapy after
severity of COVID-19 disease and block a cell process known as infection? And how will cancer
could cooperate with vaccines to JAK-STAT signaling, which pro- patients respond to the new
prevent coronavirus infections,” duces cytokines – small proteins coronavirus vaccines?
says Sodroski. that activate immune and inflam- These are some of the issues
mation responses. JAK inhibitors being investigated in a study
COVID-19 Research in the can help reduce excess cytokine called RECOVOR led by Deborah
Cancer Clinic release, which can occur in pa- Schrag, MD, MPH, chief of Popu-
In addition to lab-based re- tients with COVID-19 infections, lation Sciences at Dana-Farber. A
search, scientists have explored causing damage to the lungs large team of investigators from
repurposing drugs used in cancer and other tissues. Richard Stone, multiple disciplines are collaborat-
treatment as potential therapies MD, chief of staff and director ing on the study, which will com-
for COVID-19 patients. Richard- of Translational Research in the pare matched pairs of patients
10 Paths of Progress 2021 Dana-Farber Cancer Institu tewith and without COVID. The goal will be analyzed for biochemical of Progression of Blood Cancers,
is to understand what factors markers associated with better where people with precursor
predispose some cancer patients or worse responses to the virus. conditions are monitored. Recent
to COVID infection, particularly in They will also search for antibod- research has shown that the im-
its severe form, as well as which ies that may have developed mune system is abnormal in peo-
patients recover more easily from in patients who recover from ple with MGUS and smoldering
the disease. Schrag says there COVID-19 and look at how long myeloma. The IMPACT study aims
is some evidence for increased the antibodies last. to determine how the immune
risk in patients with leukemia A separate study, called IM- system responds to COVID-19 in-
and lung cancer and for patients PACT, is examining what effect fection and the long-term impact
who are obese, but the inves- COVID infections and vaccina- of the virus in patients with these
tigators hope to gather more
tions have on people with blood precursor conditions.
information on risk factors among
cancer precursor conditions. Among the questions the
patients who have and haven’t
These precursor conditions, IMPACT investigators are asking
had the vaccine.
MGUS (monoclonal gammopathy are: Do people who have precur-
The RECOVOR study is being
of undetermined significance) and sor conditions also have greater
conducted in both children and
smoldering myeloma, are esti- risks for COVID-19? Who is most
adults Institute-wide and will
mated to affect about 12 million at risk for long-term symptoms
serve as a shared resource that
can be used by investigators.
people and usually don’t cause and immune complications after
RECOVOR includes detailed inter- symptoms, despite the presence infection with COVID-19?
views of patients who have had of abnormal proteins in the blood. “We are doing the IMPACT
COVID and investigates the ex- However, they have the potential study to truly understand what the
tent to which COVID has affected to progress to multiple myeloma, response of the immune system to
cancer treatment and recovery. a blood cancer. COVID is – not only to the infec-
Researchers will collect blood The study is led by Dana- tion, but also to the vaccine,”
and saliva specimens at intervals Farber’s Irene Ghobrial, MD, who Ghobrial says. “Instead of giving
six months apart. The samples founded the Center for Prevention you a hypothesis – maybe they
will respond well or not – I can
actually give you data in a few
months from now.”
“Research into why patients
with cancer are at heightened
risk of developing severe forms
of the illness is moving very
quickly,” says Ziad Bakouny, MD,
MSc, co-lead author of a report
published in December 2020 on
the intersection between COVID
and cancer. The report “gives us
an opportunity to take a step
back and take stock of what
we’ve learned – to get a sense of
the most promising directions for
patients, as well as where more
Like others at Dana-Farber, the lab of James DeCaprio, MD, adopted new safety study is needed, what we need
precautions during the pandemic. to dig deeper into.”
www.dana-farber.org 11Youth Is Served
Young-Onset Colorectal Cancer Center
builds a new model of care for young
adults with colorectal cancer
BY SAUL WISNIA
12 Paths of Progress 2021 Dana-Farber Cancer Institu teDavid Thau had been experiencing
symptoms for years: intermittent stom-
ach aches and nausea, bloody stools,
and – most recently – shortness of
breath when climbing stairs. A cardiolo-
gist could find nothing wrong with his
heart, and other doctors were similarly
stumped. So Thau ignored the pain,
until it grew so bad in June 2019 that he
wound up in the emergency room.
Alexa Morell first noticed blood in
her stool while on a weekend getaway
with friends in August 2020. She was
nervous, but her companions – a group
including several nurses assured Morell
it was likely just a hemorrhoid. After
examining her, Morell’s primary care
physician and a gastroenterologist
agreed. Relieved, Morell scheduled a
colonoscopy to confirm the diagnosis.
In the end, both Morell and Thau were
shocked by the actual cause of their
problems: They had colorectal cancer.
Thau was 34. Morrell was 29. Years
Kimmie Ng, MD, MPH, examines ago, that would have been startling, but
patient David Thau. colorectal cancer cases are steadily
www.dana-farber.org 13“An early-onset colorectal cancer diagnosis should consider cancer as a likely cause,
which can lead to long delays in
always be a ‘red flag’ for possible inherited risks diagnosis – and a more advanced
stage at diagnosis. Most young
to cancer.” patients with colorectal cancer
are diagnosed with stage III or
– Matt Yurgelun, MD IV cancer, which can be harder
to treat.
rising among men and women didn’t even know what colorectal Colorectal Cancer
under age 50. cancer was before their diagno- Screenings and Studies
“Until I got my scan results, sis,” says Kimmie Ng, MD, MPH, Colorectal cancer, defined as
the thought of cancer just never who founded the center in 2019 disease that forms in the tissue
crossed my mind,” says Thau of and serves as its director. “There of the colon, rectum, or both, is
his diagnosis. “I didn’t know the was no reason for them to neces- the third-leading cause of cancer
warning signs and, at 34, I didn’t sarily know about it, because it’s for men and women in the United
think it was a possibility. My doc- traditionally been thought of as States – and the second-leading
tors didn’t either.” a disease of older people, with cause of cancer deaths when
Dana-Farber/Brigham and a median age of diagnosis in the men and women are combined.
Women’s Cancer Center (DF/ late 60s or early 70s. And when Effective screening programs
BWCC) is working to change you’re young and otherwise for people age 50 and older have
that thinking – and the statistics. healthy, and you lead a healthy led in recent years to a steady
At its Young-Onset Colorectal lifestyle, cancer is just not on decline in both diagnoses and
Cancer Center, staff are focused your radar.” mortality rates for this group, but
on treating patients, educating This is also true, Ng says, of the opposite is happening in those
the public, and uncovering the the primary care physicians younger than age 50. The number
genetic precursors to colon and and other providers who see of men and women under age 50
rectal cancers. As they help younger patients when they first diagnosed and dying of colorectal
young survivors with family plan- seek medical attention for their cancer is growing about 2% annu-
ning, work-treatment balance, symptoms. Many providers don’t ally, and most people in this group
and other issues central to their are not being screened regularly.
age group, they are simultane- Rise in Colon Cancer The U.S. Preventive Services
ously seeking reasons why their 2030 Task Force, concerned with this
numbers are going up. 12 11% development, now recommends
Through greater awareness, 10 regular preventive screenings for
and widespread adoption of pre- those at average risk for colorec-
ventive techniques like genetic
8 2010 tal cancer beginning at age
screenings and colonoscopies,
6 5% 45 – down from age 50. Screen-
4
clinicians and researchers are ing options include stool-based
hoping to catch cancers sooner, 2 tests and colonoscopies, but the
when they’re generally more 0 American Cancer Society and the
treatable, or prevent them from By 2030, it is estimated
+90.0% among that those
20-34 under
years staff within the Colon and Rectal
developing altogether. 50 will+27%
account among 35-49
for 11% of allyears
colon
Cancer Center at DF/BWCC – of
cancer cases. This represents a 90%
“We hear over and over from increase since 2010 among men and which the Young-Onset Center is
the very many young patients women ages 20-34, and a 27.7% spike a part – cite colonoscopies as the
whom we’re seeing now that they among those 35-49. best way to prevent colorectal
14 Paths of Progress 2021 Dana-Farber Cancer Instituteto take.”
Environmental factors, includ-
ing obesity and a sedentary life-
style, are also very strongly linked
to colorectal cancer, but Ng says
she doesn’t believe these in and
of themselves are the sole cause
of the rise in under-50 diagno-
ses – since the vast majority of
patients seen in the young-onset
clinic at DF/BWCC are healthy
Kimmie Ng, MD, MPH (on screen), with a patient during a virtual visit.
and active, and consume a good
diet. A rise in the use of antibi-
cancer and detect the disease at Another step aimed at sav- otics by younger people, and
an early stage. ing lives: research into possible a vitamin D deficiency due to
The 2020 death of actor Chad- genetic causes for colorectal increased time spent indoors, are
wick Boseman from colon cancer cancer – including those with an other possibilities.
at age 43 brought much-needed inherited risk. According to Matt “One of the biggest hypotheses
attention to colorectal cancer, Yurgelun, MD, a medical oncolo- is related to the microbiome, the
and the fact that younger, healthy gist and expert in cancer genetics trillions of organisms that live in
people can develop it. Despite at DF/BWCC, one in six individuals our gut and profoundly impact
being in treatment for four years, diagnosed before age 50 has an a variety of different chronic
the “Black Panther” star was in identifiable inherited predisposi- diseases,” explains Ng. “Diet
excellent physical shape. He also tion to colon or rectal cancer. In and lifestyle very closely shape
kept his condition hidden from order to hunt down these precur- our microbiome, which is located
fans and many friends, underscor- sors, each person seen in the right where colon cancers de-
ing what clinicians and patients Young-Onset Center is offered velop in our gut. The microbiome
agree is another challenging as- genetic testing. If a relevant is thought to have a major role in
pect of colorectal cancer: It is not genetic alteration is found, why colon cancers happen, and
something many people feel easy they are then seen by Yurgelun we’re trying to further explore
talking about – even superheroes. or another physician at Dana- how exactly it could be contribut-
“We need to normalize conver- Farber’s Center for Cancer ing to young-onset disease.”
sations about your bowel habits Genetics and Prevention.
and symptoms,” says Ng. “By “An early-onset colorectal Friends and Family
talking about colorectal cancer on cancer diagnosis should always (Planning) for Colorectal
a national stage, which happened be a red flag for possible inherited Cancer Patients
when Chadwick Boseman died, risks to cancer,” says Yurgelun. While the Young-Onset Center
we can help more people learn “For individuals with specific looks to provide answers and
about this disease, open up about forms of inherited cancer risk, prevent future cases, it also
their symptoms, there may be some particular serves as a source of informa-
and get them changes to their treatment, like tion and assistance for current
seeking medi- targeted therapies or specific patients. With access to a series
cal attention surgical interventions, that should of ongoing events and resources,
earlier. That be considered for treatment of survivors like Morell – the mother
will save their colorectal cancer, as well as of a toddler – can find under-
Colon cancer cell more lives.” steps for at-risk family members standing in the waiting room and
www.dana-farber.org 15Who Should Be Screened for Colorectal Cancer? Matt Yurgelun, MD Using genetic screening to parent or sibling with colorectal colorectal cancer, beyond inher- identify an inherited cancer cancer should begin their own ited genetics,” says Yurgelun, predisposition syndrome can colorectal cancer surveillance who directs Dana-Farber’s Lynch uncover other cancer risks, and no later than age 40, or 10 years Syndrome Center. “Many individu- help patients mitigate those risks younger than the earliest colorec- als with inherited risks of colorec- through appropriate surveillance tal cancer diagnosis in the family, tal cancer do not develop it. On or other means. According to whichever is earlier. Individuals the other hand, some individuals DF/BWCC oncologist and genetics with specific forms of inherited lacking identifiable inherited risk expert Matt Yurgelun, MD, it can colorectal cancer risk, includ- syndrome are nonetheless struck also help to prevent cancer in ing Lynch syndrome – a genetic with a young-onset colorectal at-risk family members. condition associated with higher cancer diagnosis. Even in cases where a specific risk – should begin colorectal “As we come to understand the inherited predisposition syndrome cancer surveillance even earlier, factors that modify genetic risks, cannot be found for an individual and often need screening for other including behavior, diet, lifestyle, with young-onset colorectal can- forms of cancer. and immunologic factors,” he cer, Yurgelun says, it is important “We’re just starting to scratch adds, “we can better personalize for the patient’s family members the surface of other factors that our risk assessment and preven- to get screened. Anyone with a influence risk for young-onset tion strategies.” 16 Paths of Progress 2021 Dana-Farber Cancer Institu te
the exam room.
Mary-Brent Brown, the center’s
research and program coordina- An estimated 17,930 people
tor, is the go-to source for pa- under age 50 in the US
tients and families. Social worker
Karen Fletcher, MSW, MPH, who developed colorectal cancer
specializes in the psychosocial in 2020, more than 12 percent
needs of younger adults and
their caregivers, leads a series of
of all new cases.
monthly brown-bag lunches for
active and past patients. Started
by her predecessor, Katelyn Mac-
Dougall, MSW, LICSW, as regular
events held on Dana-Farber’s Colorectal cancer is most frequently diagnosed at ages 65-74, but cases among
young adults (ages 20-49) have steadily risen since the mid-1990s – even while
Longwood campus, the lunches
incidences adjusted for all ages have dropped annually in recent years.
moved to Zoom at the start of the
COVID-19 pandemic. experts – moderated by Ng – on
For the past two years, the cen- the latest clinical trials, microbi-
ter has marked Colorectal Cancer ome research, and immunother-
Awareness Month (March) by apy options. Attendees had the
hosting free educational events opportunity to make connections
for patients and their loved ones. during breakout sessions and
The 2021 series, held on Zoom other online activities.
over six March afternoons, Such offerings have played a
featured a keynote event with pivotal role for Thau in his treat-
Professor Ibram X. Kendi, a leader ment and recovery. He met with
in antiracist research and a stage MacDougall during each of his
IV colorectal cancer survivor. 12 chemotherapy sessions at Mary-Brent Brown, program manager
There were also sessions on Dana-Farber from July to De- of the Young-Onset Colorectal
living well, diet and exercise, and cember 2019, and credits her for Cancer Center
insights from a panel of research helping him feel more comfortable ing about starting a future family
discussing his condition. Attend- with my wife, Lisbeth, and right
Rise in Rectal Cancer ing Fletcher’s brown-bag lunches away they told me they felt that
provides an opportunity to swap chemo may potentially damage my
2030 stories with people who can re-
25
22% sperm. So, before I even began
20
late to his treatment side-effects, treatment, I banked some sperm.
and his diagnosis prompted him “Your head is spinning when
15 2010 to encourage his younger brother you’re that young and find out you
10 9% also get screened. have cancer,” he adds. “But the
5
Thau’s most advantageous mo- more I learned about colorectal
ment at the Young-Onset Center, cancer, the more I saw how many
0
however, came early on. people my age were getting it.
+124.2%
For rectal among
cancer, 20-34for
diagnoses years
men
+46.0% among 35-49 years “The center was incredibly That’s why awareness and screen-
and women under 50 are expected to
more than double between 2010-2030. helpful on the front end, helping ing and other steps like family
The rise is especially pronounced me prepare for what I needed to planning are so critical. This is a
(124.2%) among those ages 20-34. do,” Thau explains. “I was think- preventable disease.”
www.dana-farber.org 17The Cellular
Therapies Revolution
Dana-Farber scientists power ongoing
innovation in cell therapies for cancer
BY ROBERT LEVY
I
t’s been more than 130 close quarters combat would
years since scientists first work to the advantage of the
brought tumor tissue into immune system, honed by eons
focus under a microscope of evolution to detect and destroy
lens. Little did they imag- cancer cells. But cancer cells
ine that what they saw have used the same eons to
harbored the elements develop evasive maneuvers
of a powerful form of against an immune attack:
cancer therapy. disguising themselves as normal
Tumors are hardly cells, converting immune cells
models of harmony. They into promoters of tumor growth,
contain cancer cells by and deploying a variety of other
the millions, side by side strategies to foil or fool the
with cells from their arch enemy, immune system’s radar.
the immune system. Ideally, such To overcome cancer’s trickery,
18 Paths of Progress 2021 Dana-Farber Cancer Institu teThe making of a CAR T cell: the forefront of testing and devel-
In the illustration at left, a virus oping many of these therapies,
(with spikes) carrying specific the first clinical trial of an experi-
DNA instructions enters an
immune system T cell (the large
mental CAR T-cell therapy opened
blue sphere). Here, the virus in 2015. As of early 2021, five com-
releases the coils of DNA into the mercially-produced CAR T-cell
cell. The T cell will use them to therapies have been approved by
make proteins that help it target the Food and Drug Administra-
the patient’s cancer cells.
tion (FDA) as standard treatment
for adults with aggressive B-cell
lymphoma or mantle cell lym-
phoma, children and young adults
with aggressive B-cell lymphoma
or acute lymphoblastic leukemia
(ALL), and, most recently, adults
with follicular lymphoma and
multiple myeloma.
Impressive as this list is, it’s
destined to grow. Behind it is a
research pipeline stocked with
CAR T and other cell therapies
for a wide range of cancer types
– approaches in every stage of
development from initial labora-
tory studies to tests in model
systems to final-stage clinical
trials in patients. Dana-Farber
researchers are involved all along
the way, with chemical biologists
scientists have developed a new equipping a patient’s own immune
form of therapy built from immune system T cells with a receptor
cells themselves. Known as cell that binds to tumor cells and
therapy – or, more formally, im- spurs an immune attack on them.
mune effector cell (IEC) therapy It has been joined by a platoon
– the approach uses genetic of other cell therapies – natural
engineering and other techniques killer (NK) cells, engineered T
to upgrade immune cells’ ability cell receptor (TCR) therapy, and
to identify, surveil, and ultimately tumor-infiltrating lymphocytes
destroy malignant cells. (TILs) – all designed to improve on
The best-known form of IEC the immune response bequeathed
therapy, largely because it was by nature.
the first out of the gate, is chi- It is hard to overstate the speed
meric antigen receptor or CAR at which the field is moving. At
T-cell therapy, which is created by Dana-Farber, which has been at Sarah Nikiforow, MD, PhD
www.dana-farber.org 19developing new ways of engi- are the focus of a tremendous Cell Therapy Adds a New
neering cells, the Connell and amount of research at both Option to Cancer Treatment
O’Reilly Families Cell Manipula- the basic-science and clinical Cell therapy is often said to
tion Core Facility (CMCF) making research level,” says Sarah be a new, “fifth pillar” of cancer
CAR T cells for clinical trials, and Nikiforow, MD, PhD, techni- treatment – joining surgery, radia-
physician-scientists leading trials cal director of Dana-Farber’s tion therapy, chemotherapy, and
of new therapies. As 2021 began, Immune Effector Cell Therapy targeted therapy in the cancer
the Institute was conducting 20 program. “For all the benefit armamentarium – but it actually
trials of CAR T-cell therapies, two they’ve shown and for all the represents a more fundamental
of NK cell therapies, two of TCR progress we’ve made, we’re still change. For the past hundred
therapies, and two of TILs. in the early stages of exploring years, human intervention, in
“Immune effector cell therapies their potential.” the form of surgery, radiation,
Dana-Farber’s Connell-O’Reilly Core Facility
Like a great teacher or pilot, cell cell therapies, as well as making
therapies are made, not born. Al- tumor vaccines and processing
though they derive from living things blood-forming stem cells for trans-
– immune system cells – they are plantation. In 2020, the facility pro-
inherently a manufactured product, cessed cells for more than 900 adult
made by enhancing the cells’ and pediatric stem cell transplants
ability to identify, attack, and kill and supported more than 60 clinical
cancer cells. trials involving cell therapies.
Creating such therapies requires While most CAR T-cell therapies
Jerome Ritz, MD
not only a high degree of technical are made by commercial labs, the
expertise, but also a facility de- ability to produce them in-house is manufacturing these cells on a large
signed to meet exacting standards a significant advantage, says CMCF scale for patients enrolled in the first
for product purity, consistency, and Executive Director Jerome Ritz, clinical trials evaluating the safety
safety. At Dana-Farber, the Connell MD. “For a commercial product, the and efficacy of these products,” Ritz
and O’Reilly Families Cell Manipula- patient’s cells need to be shipped to remarks. “There’s a critical role for
tion Core Facility (CMCF) enables the an outside facility for manufacture academic facilities like ours in sup-
Institute to provide the latest cell- and testing and then shipped back. porting early-phase clinical trials.”
based therapies to patients while It can take weeks or months to The CMCF has recently invested in
creating new therapies for study in complete the process. At the CMCF, technology to speed up the manu-
clinical trials. we can have a CAR T-cell therapy facture of CAR T and other cellular
Since the lab was established in ready to infuse within seven to therapies. Four CliniMACS Prodigy in-
1996, the CMCF has grown rapidly eight days.” struments, which automate the entire
and is now located in a new 30,000 The CMCF is a particular asset process of CAR T-cell therapy produc-
square-foot facility dedicated to for early-phase clinical trials. tion, are in use for multiple trials of
supporting novel cellular therapies. “When a potential cell therapy new therapies. “Automated systems
The CMCF produces CAR T cells, emerges from the laboratory, we make more consistent products and
memory-like natural killer (mlNK) work with investigators and local reduce the time and effort involved by
cells, and a variety of other adoptive companies to develop a process for half to two-thirds,” Ritz says.
20 Paths of Progress 2021 Dana-Farber Cancer Institu teYou can also read
