Immunologic checkpoint blockade and adoptive cell transfer in cancer therapy dream team
Dream Team Leaders
James P. Allison, Ph.D., chairman in the department of immunology, director of the immunotherapy platform, and co-director of the David H. Koch Center for Applied Research of Genitourinary Cancers at The University of Texas MD Anderson Cancer Center.
“The goal of our Dream Team is to expand, optimize and explore combinations of two novel immunotherapies, immune checkpoint blockade and adoptive T-cell transfer. It is our dream, indeed our expectation, that by optimizing these two uniquely successful and complementary approaches, we will be able achieve durable responses in a large percentage of patients suffering from a variety of types of cancer,” said Allison.
Antoni Ribas, M.D., Ph.D., professor of medicine, surgery, and molecular and medical pharmacology, director of the tumor immunology program area at the Jonsson Comprehensive Cancer Center, and member of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles
“The patient’s own immune system can be harnessed to treat some cancers. The SU2C-CRI Dream Team grant will help develop this mode of treatment to more broadly benefit patients,” said Ribas.
Dream Team Co-leaders
Drew M. Pardoll, M.D., Ph.D., co-director of the division of immunology and hematologic malignancies and professor of the department of oncology at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University in Baltimore, Md.
“The clinical advances in immunotherapy just in the past two years have shown that these strategies indeed empower the patient’s own immune system to successfully fight their cancer. Single interventions opened the door; the future is combinatorial therapy and the synergistic expertise of our SU2C Dream Team will catalyze the development of the most innovative of combinations,” said Pardoll.
Cassian Yee, M.D., is a member of the Clinical Research Division and Program in Immunology at Fred Hutchinson Cancer Research Center; a professor of medicine at the University of Washington School of Medicine and an attending physician at the Seattle Cancer Care Alliance in Seattle, Wash.
“Adoptive T cell therapy in recent years has really come into its own. Novel strategies to generate longlasting, highly effective T cells are being developed, and in combination with new immunomodulatory agents like the checkpoint inhibitors, we can fully exploit the immune system to treat patients with cancer. We are so fortunate to have the opportunity to work with the team on these projects,” said Yee.
Research Project Description
Cancer immunologists have long hypothesized that specific interventions could stimulate and “re-educate” patients’ own immune systems to attack their cancer. In one approach of immunology-based cancer treatment, scientists use a type of white blood cell called a T lymphocyte from the patient to kill the cancer cells. These T lymphocytes have receptors (TCR) on their surface that activate the T lymphocytes and allow them to recognize and specifically target cancer cells. However, under normal biological conditions, only limited numbers of T lymphocytes are activated. Additionally, this anticancer process can be blocked by specific inhibitory molecules called checkpoints, some of which are expressed by the cancer cells themselves. Checkpoints act like the parking brake of a car, stopping the process that T lymphocytes use to kill cancer cells.
The Dream Team will focus on two approaches to overcome these obstacles. First, they will investigate checkpoint blockade where they hope to “disable the brakes.” The Dream Team will investigate the use of antibodies to remove the checkpoints, once again allowing T lymphocytes to kill the cancer cells.
To do this, they will analyze tumor samples to determine checkpoint expression in tumors before and after checkpoint blockade or adoptive cell transfer (ACT), possible synergistic treatment combinations, and biomarkers that may be able to predict response or resistance to therapy. In addition, based on previous research, the Dream Team will investigate whether a combination treatment of a specific checkpoint blockade (anti-CTLA-4) and inhibition of tumor blood vessel formation will improve patient outcomes. Furthermore, they will test the hypothesis that multiple T lymphocyte targets are expressed by tumor cells.
Second, the team will pursue multiple ACT approaches, where a large army of cancer-specific T lymphocytes is generated from a cancer patient’s samples and given back to the patient. One approach is to start from a few T lymphocytes with the desired ability to recognize and kill cancer, grow them in the laboratory, and then give them to the patient. Another way is to use gene transfer techniques to take the TCR from one T lymphocyte that is cancer-specific and insert it into many other T lymphocytes that then become cancer-specific. The team will use artificial receptors based on antibodies, termed chimeric antigen receptors (CAR) to redirect the killing ability of T cells and restrict it to cancer cells.
The Dream Team will jointly address key factors currently limiting the efficacy and wide applicability of tumor immunotherapy. The clinical impact of this project lies with the potential synergy of combining checkpoint blockade and ACT to treat a range of tumor types to improve the lives of patients with cancer.
The “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy” Dream Team consists of a multidisciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates. Besides Allison, Ribas, Pardoll and Yee, team members include:
David Baltimore, Ph.D., California Institute of Technology, Pasadena, CA
Glenn Dranoff, M.D., Dana-Farber Cancer Institute, Boston, MA
Philip D. Greenberg, M.D., Fred Hutchinson Cancer Research Center, Seattle, WA
Michel Sadelain, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, NY
Ton Schumacher, Ph.D., Netherlands Cancer Institute, Amsterdam, The Netherlands
Jedd D. Wolchok, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, NY
Robert E. Behrens, REB Investments Inc.
Debra Black, Melanoma Research Alliance
Roy Doumani, cancer survivor
Valerie Guild, Aim at Melanoma
Jonathan W. Simons, M.D., Prostate Cancer Foundation
Mary Elizabeth Williams, Salon.com
Since Stand Up To Cancer’s launch in 2008, SU2C has awarded grants to nine Dream Teams and one International Translational Cancer Research Grant. Twenty-six Innovative Research Grants have been awarded to individual young investigators. These recipients comprise more than 450 scientists from more than 85 institutions.
About Stand Up To Cancer
Stand Up To Cancer (SU2C) — a program of the Entertainment Industry Foundation (EIF), a 501(c)3 charitable organization — raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. In the fall of 2007, a group of women whose lives have all been affected by cancer in profound ways began working together to marshal the resources of the media and entertainment industries in the fight against this disease.
Members of the SU2C Executive Leadership Council (ELC) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-House Production Team; and Nonprofit Executive Ellen Ziffren. All of the ELC members were co-producers of the 2012 televised special. The late Laura Ziskin, executive producer of both the Sept. 5, 2008 and Sept. 10, 2010 broadcasts, was also a member of the ELC. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.
SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. Sixty-five institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.
About the Cancer Research Institute
The Cancer Research Institute (CRI), a nonprofit established in 1953, is the global leader in cancer immunology. Since its inception, CRI has invested hundreds of millions of dollars to support research conducted by more than 3,000 scientists and clinicians worldwide to understand the immune system and how it can be harnessed to conquer all cancers. This work has laid the foundation for nearly every major cancer immunotherapy breakthrough over the past half century.
Guided by an international panel of the world’s leading immunologists and cancer immunologists, including three Nobel laureates and 29 members of the U.S. National Academy of Sciences, CRI provides essential funding to support every stage of discovery, from laboratory investigation to clinical trials of the most promising cancer immunotherapies for patients.
CRI also sponsors a seminal international symposium on cancer immunology each year, hosts annual scientific colloquia dedicated to overcoming challenges in immunotherapy research and development, forges collaborative partnerships between academia and industry to facilitate the development pathway for novel immunotherapeutics, and presents special recognition awards to individuals who have made outstanding contributions to cancer research, patient care and public awareness.
Through its sustaining support and leadership in the field, CRI is accelerating the development of safe and effective immunotherapies that stand to revolutionize the treatment of all cancers. For more information, visit http://cancerresearch.org or follow CRI on Twitter @CancerResearch.
About the American Association Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional association dedicated to advancing cancer research and preventing and curing cancer. AACR membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.