Thursday, June 13, 2024

Lab-Created Immune Cells Promise Survival for Blood Cancer Patients

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The 2024 Warren Alpert Foundation Prize has been awarded to four scientists whose transformational discoveries led to the creation of chimeric antigen receptor (CAR) T cells, a treatment that modifies patients’ immune cells and optimizes their ability to eliminate cancer cells.

CAR T-cell therapy, the first successful example of synthetic biology used in clinical medicine, has saved the lives of tens of thousands of adults and children with blood cancers, including leukemia, lymphoma, and multiple myeloma.

The award recipients are:

  • Renier Brentjens, Katherine Anne Gioia Endowed Chair of Medicine and deputy director of Roswell Park Comprehensive Cancer Center
  • Zelig Eshhar, professor emeritus, the Weizmann Institute of Science, chair of Immunology, Division of Research & Development, Sourasky Medical Center, Israel
  • Carl June, Richard W. Vague Professor in Immunotherapy, University of Pennsylvania Perelman School of Medicine
  • Michel Sadelain, Stephen and Barbara Friedman Chair, founding director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center

The $500,000 award, to be shared among the four winners, is given by the Warren Alpert Foundation in recognition of work that has improved the understanding, prevention, treatment, or cure of human disease. The prize is administered by Harvard Medical School. The award winners will be recognized at a scientific symposium on Oct. 10 hosted by Harvard Medical School. For details, visit the Warren Alpert Foundation Prize symposium website.

“The collective work of the four scientists honored this year has propelled the treatment of blood cancers into a new era of immune therapy and added an invaluable new tool to our armamentarium,” said George Q. Daley, dean of HMS and chair of the Warren Alpert Foundation Prize scientific advisory committee. “The discoveries are a striking example of the promise of synthetic biology to redefine the way we conceive and design novel therapies.”

Significance of the work

CAR T cells are genetically engineered immune cells tailored to respond to a specific molecule found on the surface of tumor cells. These cells are a form of immunotherapy – an approach that harnesses the native ability of the immune system to fight diseases, particularly cancer. CAR T-cell therapy represents a milestone in cancer treatment. It propels cancer therapies beyond traditional chemotherapy and radiation treatments, which are often highly toxic and non-specific.

The four scientists honored with this year’s Warren Alpert Foundation Prize each played key distinct and complementary roles in developing CAR T cells and making their use in the clinic possible. Today, CAR T-cell therapies offer great hope for patients with various B-cell malignancies who have relapsed or failed to respond to other therapies. CAR T cell-based approaches could eventually be used to treat solid tumors, as well as a variety of autoimmune diseases and other conditions.

From left: Renier Brentjens, Zelig Eshhar, Carl June, Michel Sadelain

Patients whose blood cancers return after multiple rounds of chemotherapy have few options left for long-term disease control. CAR T cells have offered a new lifeline to these patients. Since 2017, six CAR T-cell therapies have been approved by the U.S. Food and Drug Administration.

“The discoveries of these researchers powerfully exemplify the mission of the Warren Alpert Foundation. Their achievements in the lab harnessed genetic engineering and immunology to create a clinical treatment that enables the treatment of disease and improves human life,” said David M. Hirsch, director and chair of the board of The Warren Alpert Foundation.

Evolution of the science paving the way to CAR T-cell therapy

More than a century ago, physicians observed that patients with cancer who also had bacterial infections experienced curious improvement of their cancers. This observation was the first clue of the immune system’s possible role in cancer recognition and eradication. Physician William Coley in the late 19th century famously treated patients by injecting streptococcal bacteria into their tumors, causing the cancers to shrink.

Building on these early observations, over the past several decades scientists have elucidated exactly how the immune system recognizes and destroys cancer cells. These insights have led to the development of several forms of cancer immune therapy.

Cytotoxic T cells are a major player in the immune system’s ability to detect and fight cancer. They recognize nascent cancer cells and kill them by delivering toxic proteins. However, cancer cells have developed their own tools to evade the immune system, using biological tricks to avoid detection or co-opting immune cells to promote tumor growth.

The collective discoveries of the four researchers led to the design of optimized immune cells that combine T cells’ cancer-killing ability with the specificity of antibodies to spot a desired target – in this case, tumor cells – and disarm it.

Since the first approval of CAR T cells for use in children and young adults with acute lymphoblastic leukemia, CAR T-cell therapies have shown efficacy and have been approved in adults, for other forms of cancer, including large cell lymphoma, follicular lymphoma, mantle cell lymphoma, as well as acute lymphoblastic leukemia. More recently, newer CAR T-cell therapies targeting different molecules have been approved to fight multiple myeloma.

Researchers in both academia and industry continue to explore new ways of using CAR T cells to treat other diseases. These include cancers that form solid tumors, which make up the majority of cancer types, as well as some inflammatory and autoimmune conditions.

From the winners

“Receiving the Warren Alpert Foundation Prize is an immense honor. It has been an incredible privilege to lay the foundation for a field with so much untapped promise. To earn this prestigious distinction alongside Drs. Sadelain, June, and Eshhar for work recognized by our peers in medical science makes this moment especially rewarding.” – Renier Brentjens

“It is with great gratitude and honor that I receive the prestigious Warren Alpert Foundation Prize alongside my respected partners. Our long and interesting road together led to a breakthrough technology that allows patients for whom there was no cure to receive treatment and remedy. For this I am extremely proud because every researcher’s aim is to find aid for those in need.” – Zelig Eshhar

“This is such a meaningful recognition by the Warren Alpert Foundation Prize for our work in the field of CAR T-cell therapy. It’s truly gratifying and motivating for the entire team in my laboratory and for our clinical team. This will help us continue to attract the best and brightest young minds to this area of research and to make a difference for patients now and in the future.” – Carl June

“The Warren Alpert Foundation Prize is bestowed by an eminent scientific committee. It is humbling to be recognized by these peers and a tremendous honor to be associated with this prize and the earlier laureates who comprise so many towering figures of medical research. I am immensely grateful to Renier Brentjens, Isabelle Rivière, and our teams for making this journey so rewarding for all.” – Michel Sadelain

The prize

The Warren Alpert Foundation Prize recognizes the research of scientists throughout the world. Including the 2024 prize, the foundation has awarded more than $8 million to 83 individuals. Since the inception of the award in 1987, 14 honorees have gone on to receive Nobel prizes.

The 2023 Warren Alpert Foundation Prize was awarded to David J. Lipman for his visionary work in the conception, design, and implementation of computational tools, databases, and infrastructure that transformed the way biological information is analyzed and accessed freely and rapidly around the world.

Other past recipients include:

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