[January 30, 2018] |
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ADDING MULTIMEDIA Stand Up To Cancer Announces $11M Collaborative, Multi-Disciplinary Research Program; Microsoft Will Bring Power of AI to Investigate Immune System Response to Cancers
Stand Up To Cancer (SU2C) announces today a "Convergence (News - Alert) 2.0" research
initiative that awards $11 million to seven multi-disciplinary research
teams to investigate immune system response to cancers. The
multi-institutional teams being announced today at SU2C's Scientific
Summit draw from the nation's top academic research centers and will
have access to Microsoft (News - Alert) Research's experts in machine learning and
artificial intelligence.
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Each team will be comprised of experts in life sciences, physical
sciences, mathematics and engineering and will have the opportunity to
work collaboratively with Microsoft's machine learning experts to
discover key aspects of the interaction between cancer and the immune
system that can lead to the development of new treatments.
In addition to the significant support from Microsoft, the Lustgarten
Foundation for Pancreatic Cancer Research committed $1.76 million in
funding, and the Society for Immunotherapy of Cancer (SITC) will provide
$1 million to support post-doctoral fellows on five of the seven teams,
providing an opportunity for early-career scientists to work with
leading researchers.
"It's an exciting new time in cancer research. Investigation of the
human genome and individual tumor genetics is producing mammoth amounts
of data that need to be interpreted in order to deliver the best
possible cancer care," said Phillip A. Sharp, PhD, chairman of the SU2C
Scientific Advisory Committee and institute professor at the Koch
Institute for Integrative Cancer Research at the Massachusetts Institute
of Technology. In 2011, Dr. Sharp co-authored the seminal MIT white
paper, "The Third Revolution (News - Alert): The Convergence of the Life Sciences,
Physical Sciences, and Engineering."
"Our first convergence research cohort, announced in 2016, established
the effectiveness of a broad multidisciplinary approach for creating
models for how cancer grows and reacts to treatment," said Arnold J.
Levine, PhD, chair of the SU2C Convergence Initiative, co-vice chairman
of the SU2C Scientific Advisory Committee and Professor emeritus,
Institute for Advanced Study. Through the collaboration with Microsoft
and using well characterized, de-identified patient data, we will look
at how individuals vary in their immune responses to an array of
therapies. And we will create standardized measurement protocols that
may speed the development of cancer therapies and ultimately save lives."
Working with Microsoft machine learning experts, SU2C researchers will
be able to study terabytes of data derived from multiple data sets,
including information on the patient's genome, imaging studies, medical
and medication records, among other data. Over the course of three
years, the Stand Up To Cancer Convergence 2.0 Research Teams will
explore a host of factors that may contribute to a patient's response to
a specific regimen, including: DNA mismatch repair, tumor-specific
proteins from mutated genes, cytokine function and natural killer cells.
These therapies will be studied both when they do work, and when they
don't, to inform medical practice.
"We're thrilled to collaborate with Stand Up To Cancer on this amazing
opportunity to merge Microsoft's state-of-the-art machine learning
expertise, our work with the intelligent cloud, and our world-class
research capabilities with their network of renowned researchers and
clinicians - all to accelerate progress in cancer immunotherapy.
Ultimately, we aim to provide patients with targeted therapies which
control cancer with less damage than current therapies," said Dr.
Jennifer Chayes, Technical Fellow & Managing Director, Microsoft
Research New England, New York, Montreal. "All of us at Microsoft
Research want to empower cancer researchers and ultimately cancer
patients. Our goal is for patients to have more effective and less
damaging therapies available, which will increase both their longevity
as well as their quality of life."
Dr. Levine will announce the seven teams that are receiving the awards
at the eighth annual Scientific Summit, organized by the American
Association for Cancer Research (AACR) in its capacity as the Scientific
Partner of SU2C.
The teams chosen by the Convergence 2.0 Selection Committee and SU2C
Scientific Advisory Committee are:
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Computational deconstruction of neoantigen-TCR degeneracy for
cancer immunotherapy
Additional Support: Lustgarten
Foundation; SITC Team Leaders: Benjamin Greenbaum, PhD, at
the Icahn School of Medicine at Mount Sinai Hospital; Vinod
Balachandran, MD, Memorial Sloan Kettering Cancer Center Team
Members: Marta Luksza, PhD, Icahn School of Medicine at Mount
Sinai; Eileen M. O'Reilly, MD, David M. Rubenstein Center for
Pancreatic Cancer Research; Jedd Wolchok, MD, PhD, Memorial Sloan
Kettering Cancer Center Collaborators: Nina Bhardwaj, MD,
PhD, Icahn School of Medicine at Mount Sinai; Curtis Callan, PhD,
Princeton University; Timothy Chan, MD, PhD, Memorial Sloan Kettering
Cancer Center; Simona Cocco, PhD, Ecole Normale Supérieure; Jeffrey
Drebin, MD, PhD, Memorial Sloan Kettering Cancer Center; Anthony Gill,
MD, Professor of Surgical Pathology, University of Sydney; Christine
Iacobuzio-Donahue, MD, PhD, Memorial Sloan Kettering Cancer Center;
Dmitry Krotov, PhD, Member, Institute for Advanced Study; Taha
Merghoub, PhD, Memorial Sloan Kettering Cancer Center; Rémi Monasson,
PhD, Centre National de la Recherche Scientifique; Thierry Mora, Ecole
Normale Supérieure; Aleksandra Walczak, PhD, Ecole Normale Supérieure Project
Summary: The team will build on the work started under a
Convergence 1.0 grant but further explore the underpinnings that
constitute pancreatic survivorship. By looking at the few individuals
who survive pancreatic cancer for long periods of time, the team
identified an initial set of high-quality neoantigens, or protein
tags, on cancer cells that the immune system recognizes. This project
will continue the work to understand what makes a high-quality
neoantigen and how the microbiome influences how the immune system
recognizes it, with the goal of developing a method for creating
vaccines to treat pancreatic cancers. This research will have a
significant impact on understanding neoantigen-T cell immunobiology
and could improve the treatment prospects of pancreatic cancer
patients.
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Single-Cell Functional Multi-Omics to Characterize and Monitor CAR
T Therapy
Additional Support: SITC Team Leader:
Rong Fan, PhD, Yale University; Team Members: Stephanie
Halene, MD, PhD, Yale School of Medicine and Yale University; Carl H.
June, MD, University of Pennsylvania Perelman School of Medicine;
Pablo G. Cámara, PhD, University of Pennsylvania Perelman School of
Medicine; J. Joseph ("Jos") Melenhorst, University of Pennsylvania
Perelman School of Medicine Project Summary:
Immunotoxicity and autoimmune-like response is a significant problem
hindering widespread use of cancer immunotherapies. Major players in
the immune response are cytokines, which are substances secreted by
some immune cells to affect other cells in response to a signal, e.g.,
recognition of a foreign body. To understand this response, the full
spectrum of cytokine functions in a pre-infusion setting will be
assessed and matched with patient responses to treatment with the
chimeric antigen receptor (CAR) T therapy. Afterward, the function of
the infused CAR T cells will be assessed to determine the mechanisms
of efficacy and/or immune toxicity. The team also proposes identifying
molecular characteristics underlying therapeutic efficacy and toxicity
of CAR T therapy, and biomarker discovery by using computational
models and machine learning that look at the data. If successful, this
will create a "tool" that clinicians can use to mitigate patient risk
associated with CAR T therapies while improving the chances of
therapeutic success.
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Integrating Experimental and Computational Pipelines to Develop
Biomarkers of Tumor Cell Resistance to NK Cells
Team
Leader: Constantine Mitsiades, MD, PhD, Dana-Farber Cancer
Institute Team Members: Michal Sheffer, PhD, Dana-Farber
Cancer Institute; Ricardo de Matos Simoes, PhD, Dana-Farber Cancer
Institute; Aedin Culhane, PhD, Dana-Farber Cancer Institute; Todd
Golub, MD, Broad Institute of MIT and Harvard; Aviad Tsherniak, MSc,
Broad Institute of MIT and Harvard; Christopher Mader, PhD; Broad
Institute of MIT and Harvard; Jennifer Roth, MSc, MBA, Broad Institute
of MIT and Harvard Collaborators: Jacob Laubach, MD,
Dana-Farber Cancer Institute; Paul G. Richardson, MD, Dana-Farber
Cancer Institute; Rizwan Romee, MD, Washington University School of
Medicine in St. Louis; Jerome Ritz, MD, Dana-Farber Cancer Institute;
Lotte Wieten, PhD, Maastricht University Medical Center, Netherlands;
Richard Groen, PhD, VU Medical Center, Amsterdam, Netherlands Project
Summary: Natural killer (NK) cells, white blood cells that play a
role in viral response, have potent anti-tumor cell killing
properties. Moreover, NK cells are not inhibited by many of the
strategies cancer cells use to evade the immune system. This team
hypothesizes that the genetic make-up of a tumor may serve as a basis
to target its destruction by NK cells. To identify biomarkers that are
responsible for tumor cell sensitivity or resistance to NK cells, the
team will use computational approaches. The team members will also
explore novel interaction patterns based on NK responses by using
tools such as CRISPR screens. Finally, these biomarkers will be
validated on different experimental platforms such as patient-derived
organoids and high-throughput systems to quantify tumor cell responses
to immune effector cells. Results from this research could have an
impact on models used to study a wide range of cancers.
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Correlating Immunological Health to Cancer Susceptibility
Additional
Support: SITC Team Leader: Mark Davis (News - Alert), PhD, Stanford
University Team Members: Stephen Quake, PhD, Stanford
University; Thomas Montine, MD, PhD, Stanford University; Kari Nadeau,
MD, PhD, Stanford University; David Furman, PhD, University of Buenos
Aires, Argentina Project Summary: A preliminary analysis
of over 450 adults showed that the immune response to influenza
vaccine may be correlated with cancer susceptibility. In a small
subset of elderly subjects who received the influenza vaccine,
subjects with less robust immune response were more likely to develop
and succumb to cancer. This team will correlate the varying immune
cell (T- and B-cell populations) repertoires in individual patients
with cancer susceptibility, comparing the results to a separate cohort
of patients who are immune deficient. Even partial success could lead
to testable signatures for cancer prediction.
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Connecting Immune Health and Tumor Biology in Gynecologic Cancers
Additional
Support: SITC Team Leader: John Wherry, PhD,
University of Pennsylvania Team Members: Claire Friedman,
MD, Memorial Sloan Kettering Cancer Center; Robert Burger, MD, FACOG,
FACS, The Hospital of the University of Pennsylvania; Daniel Powell,
PhD, University of Pennsylvania; Shelley Berger, PhD, Perelman School
of Medicine University of Pennsylvania; Erica Carpenter, MBA, PhD,
Perelman School of Medicine University of Pennsylvania; Dana Pe'er,
PhD, Memorial Sloan Kettering Cancer Center; Dmitriy Zamarin, MD, PhD,
Memorial Sloan Kettering Cancer Center; Travis Hollman, MD, PhD,
Memorial Sloan Kettering Cancer Center Collaborators: Benjamin
Greenbaum, PhD, Icahn School of Medicine at Mount Sinai; David Ting,
MD, Massachusetts General Hospital/Harvard Medical School; Ernest
Fraenkel, PhD, Massachusetts Institute of Technology Project
Summary: Mismatch repair (MMR)-deficiency, the inability to repair
base pairing within the DNA helix, can give rise to a weakened DNA
structure, which leads to the accumulation of mutations. The response
to immune checkpoint inhibitors has been varied in gynecologic
cancers, possibly due to the number of mutations carried by each tumor
cell (mutational burden). The team hypothesizes that the tumors with a
high mutational burden fail to respond to checkpoint inhibition
because of an immune dysfunction that is based on the mechanism for
the MMR deficiency. The team plans to initiate two clinical trials
that will test whether a) tumor-intrinsic factors affect the response
to checkpoint inhibition; b) baseline immune function and quality
affects response to checkpoint inhibition; and c) on-treatment blood
markers may reflect the tumor-immune interaction. Understanding the
mechanism that leads to this phenomenon has the potential to
dramatically affect those patients who do not respond to current
treatments.
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Responders and Non-responders to Endometrial Cancers with Mismatch
Repair
Team Leader: Alessandro Santin, MD, Yale
University School of Medicine Team Members: Ludmil
Alexandrov, PhD, University of California San Diego; Akiko Iwasaki,
PhD, Yale University School of Medicine; and Stefania Bellone, PhD,
Yale University Collaborator: Richard Lifton, MD, PhD,
President of Rockefeller University Project Summary:
Researchers do not know why only about one-half of all patients with
mismatch repair deficient, MSI-high(h) metastatic/recurrent tumors
respond to anti-PD1 treatment. The team will develop and validate a
novel computational method to assess DNA damage and tumor mutational
burden using next-generation sequencing data. Once validated, the
approach will be applied to an ongoing trial for patients with
endometrial cancer treated with Pembrolizumab. The team hopes to be
able to predict the patients who will have side effects to checkpoint
therapies, predict antigens from T cell receptor sequences, and
determine neoantigens that are expressed by tumors that are recognized
by the immune system in an HLA-dependent fashion. Identification of
the patients who will have side effects will allow for modification of
treatment to mitigate the adverse effects.
-
Using Artificial Intelligence to predict molecular pathways and
clinical outcomes
Additional Support: SITC Team
Leader: Ernest Fraenkel, PhD, Massachusetts Institute of Technology Team
Member: Regina Barzilay, PhD, Massachusetts Institute of Technology Collaborators:
John Wherry, PhD, University of Pennsylvania; Claire Friedman, MD,
Memorial Sloan Kettering Cancer Center; Constantine Mitsiades, MD,
PhD, Dana-Farber Cancer Institute; Todd Golub, MD, Broad Institute of
MIT and Harvard; Jerome Ritz, MD, Dana-Farber Cancer Institute Project
Summary: Recent successes in cancer immunotherapy have raised high
hopes that these approaches can be expanded to more cancer types and
to more patients. However, there are many unmet challenges ahead that
will require dramatically new approaches. For example, determining
which patients are most likely to benefit from a particular
immunotherapy may require integrating diverse types of data (such as
lab values) or observational data that are captured in the text of an
electronic medical record. As there are no established methods for
such complex challenges, this team will develop innovative solutions
based on approaches integrating deep, multi-omic data, machine
learning, and natural language processing.
# # #
About Stand Up to Cancer
Stand Up To Cancer (SU2C) raises funds to accelerate the pace of
research to get new therapies to patients quickly and save lives now.
SU2C, a division of the Entertainment Industry Foundation (EIF), a
501(c)(3) charitable organization, was established in 2008 by film and
media leaders who utilize the industry's resources to engage the public
in supporting a new, collaborative model of cancer research, and to
increase awareness about cancer prevention as well as progress being
made in the fight against the disease. As SU2C's scientific partner, the
American Association for Cancer Research (AACR) and a Scientific
Advisory Committee led by Nobel (News - Alert) Laureate Phillip A. Sharp, PhD, conduct
rigorous, competitive review processes to identify the best research
proposals to recommend for funding, oversee grants administration, and
provide expert review of the research progress.
Current members of the SU2C Council of Founders and Advisors (CFA)
include Katie Couric, Sherry Lansing, Lisa Paulsen, Rusty Robertson, Sue
Schwartz, Pamela Oas Williams, Ellen Ziffren, and Kathleen Lobb. The
late Laura Ziskin and the late Noreen Fraser are also co-founders. Sung
Poblete, PhD, RN, has served as SU2C's president since 2011. For more
information on Stand Up To Cancer, visit www.standuptocancer.org
About the Lustgarten Foundation
The Lustgarten Foundation is America's largest private foundation
dedicated to funding pancreatic cancer research. Based in Woodbury,
N.Y., the Foundation supports research to find a cure for pancreatic
cancer, facilitates dialogue within the medical and scientific
community, and educates the public about the disease through awareness
campaigns and fundraising events. Since its inception, the Lustgarten
Foundation has directed $154 million to research and assembled the best
scientific minds with the hope that one day, a cure can be found. Thanks
to private funding, 100 percent of every dollar donated to the
Foundation goes directly to pancreatic cancer research. For more
information, please visit www.lustgarten.org
About the Society for Immunotherapy of Cancer
The Society for Immunotherapy of Cancer (SITC) is the world's leading
member-driven organization specifically dedicated to improving cancer
patient outcomes by advancing the science and application of cancer
immunotherapy. Established in 1984, SITC, a 501(c)(3) not-for-profit
organization, serves scientists, clinicians, academicians, patients,
patient advocates, government representatives and industry leaders from
around the world. Through educational programs that foster scientific
exchange and collaboration, SITC aims to one day make the word cure a
reality for cancer patients everywhere. To learn more, visit www.sitcancer.org
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