Five scientists to be honored with the 2017 Warren Alpert Foundation Prize will share their stories at the Warren Alpert Foundation Prize Symposium Oct. 5 at Harvard Medical School.
The scientists are receiving the accolade for critical discoveries in the field of cancer immunology. Their work elucidated mechanisms in cancer’s ability to evade immune recognition and destruction. Their findings profoundly altered the understanding of disease development and treatment and led to the development of effective immune therapies for several types of cancer.
The symposium will also feature invited speaker Michael Atkins, the deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC, and professor of oncology and medicine at Georgetown University School of Medicine, as well as HMS Dean George Q. Daley. Joan Brugge, an HMS professor of Cell Biology and director of the Harvard Ludwig Cancer Center, will moderate the symposium.
The 2017 award recipients are:
- James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center
- Lieping Chen, United Technologies Corporation Professor in Cancer Research and professor of immunobiology, of dermatology and of medicine, Yale University
- Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School
- Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University
- Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women's Hospital
“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”
The honorees will share a $500,000 prize.
The Warren Alpert Foundation, in association with Harvard Medical School, recognizes trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award honors discoveries that hold the promise to change our understanding of disease or our ability to treat it.
The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also gone on receive a Nobel Prize.
“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn't honor more worthy recipients for the Warren Alpert Foundation Prize.”
The 2017 award: Unraveling the mysterious interplay between cancer and immunity
Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.
Each of the five honorees identified key pieces of the puzzle.
The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.
Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.
A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.
A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.
Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.
Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.
The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.
A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.
Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.
Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.
Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.
