MSK Immunotherapy — Timeline of Progress

Timeline Transcript

Timeline of Progress

In 1893, surgeon William Coley began treating cancer patients with a mixture of heat-killed bacteria (“Coley’s toxins") after noticing that patients with bacterial infections sometimes saw their tumors shrink. Experts today agree that many patients benefited from this treatment. Dr. Coley, who was for many years head of the bone tumor service at Memorial, is now considered to be the “Father of Cancer Immunotherapy.”

—Cancer immunosurveillance hypothesis proposed

Physician and future MSK president Lewis Thomas and immunologist Macfarlane Burnet propose the cancer immunosurveillance hypothesis — the idea that the immune system routinely patrols and protects the body from cancer. Only when these mechanisms fail does a person develop cancer. This idea is the intellectual foundation for the field of tumor immunology.

—Leukemia virus discovered

Virologist Charlotte Friend, while working at the Sloan Kettering Institute, identifies a virus that causes leukemia in mice. Her work lends strong support to the controversial idea that viruses can cause cancer. The virus she discovered is now known as the Friend leukemia virus.

—Studies of BCG launch modern era of tumor immunology

MSK scientists Lloyd Old and Donald Clarke, along with Baruj Benacerraf of New York University, publish a paper in Nature on bacillus Calmette-Guérin (BCG), a weakened form of the bacteria that cause tuberculosis. Mice injected with BCG developed resistance to the growth of implanted tumors. This is the first direct demonstration that the body’s immune defenses can be marshaled against cancer. Dr. Old is considered the "Father of Modern Tumor Immunology."

—Viral cause of nasopharyngeal cancer uncovered

Tumor immunologist Herbert Oettgen and colleagues identify antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer, suggesting a viral cause of this disease. Though a surprising discovery at the time, we now know that several cancers are caused by viruses.

—First successful bone marrow transplant from a sibling performed

Physician-scientist Robert Good, future director of SKI, administers the first successful bone marrow transplant from a sibling, permanently curing a boy who was born with severe combined immunodeficiency ("boy in the bubble syndrome"). Dr. Good also made groundbreaking contributions to our understanding of the thymus gland and the tonsils, two important immune organs.

—First bone marrow transplant from an unrelated donor performed

MSK pediatric oncologist Richard O'Reilly and SKI director Robert Good perform the first bone marrow transplant from an unrelated donor. This opens up the possibility of a transplant for the majority of patients, who lack a matched brother or sister. Bone marrow transplantation is a standard treatment today for some blood cancers. It is considered an immunotherapy because immune cells from the donor kill cancer cells in the recipient.

—Cancer-killing immune molecule discovered

Lloyd Old, Elizabeth Carswell, and colleagues identify tumor necrosis factor (TNF), a powerful immune system molecule that causes tumors to hemorrhage and die. TNF is produced by immune cells in response to bacterial products and is believed to underlie the anticancer effect of Coley’s toxins. It is the first immune system molecule shown to have a direct effect on cancer.

—Cancer antigens identified in melanoma

Pioneering immunologist Alan Houghton identifies cancer antigens in melanoma tumors, opening avenues to targeted immune therapies. Antigens are molecular markers found on the surface of cells that the immune system recognizes as foreign or dangerous. Drugs targeting these antigens are now a standard part of cancer treatment.

—Link between immune deficiency and cancer studied

Physicians Susan Krown and Bijan Safai study the relationship between immunodeficiency and Kaposi's sarcoma, a virally caused cancer, during the early years of the AIDS epidemic. Blood from Dr. Safai’s patients is used to develop the first antibody test for HIV.

—BCG immunotherapy approved by the FDA

BCG, a bacterial vaccine, is approved by the FDA for the treatment of bladder cancer, based on results of a clinical trial conducted by urologic surgeon Harry Herr and tumor immunologist Herbert Oettgen. BCG immunotherapy is still a primary treatment for non-muscle invasive bladder cancer.

—New cancer-associated antigen identified

Lloyd Old and colleagues identify a protein recognized by “killer” immune cells that is found in many cancers, but not in most normal body cells, with the exception of the testis. This “cancer-testis” antigen, NY-ESO-1, is now being tested in cancer vaccines and other immunotherapies.

—Treatment developed to enhance immune recovery

Physician-scientist Marcel van den Brink develops a treatment to improve immune recovery and healing following bone marrow transplantation (BMT), without aggravating graft-versus-host disease (GVHD). BMT patients are susceptible to dangerous infections following transplant. Treatments to boost immune recovery must be balanced against the possibility of GVHD, in which the donor cells attack normal tissues.

—Chimeric antigen receptor (CAR) T cells developed

Michel Sadelain, Renier Brentjens, and Isabelle Rivière of MSK develop genetically engineered T cells with a chimeric antigen receptor (CAR), now a powerful way to fight leukemia and other blood cancers. CARs are hybrid proteins made up of several immune molecules joined together. This team of investigators at MSK is the first to develop this technology, and continues to refine and optimize it to treat a variety of cancers. Dr. Sadelain won the William B. Coley award in 2012.

—Genetic switch for regulatory T cells discovered

Immunologist Alexander (Sasha) Rudensky shows that Foxp3 is the genetic switch controlling regulatory T cell development. Regulatory T cells are important immune cells that prevent unwanted or excessive immune reactions. Understanding how to selectively target particular regulatory T cells to enhance the immune response to cancer is a major goal of research in cancer immunotherapy. For his work, Dr. Rudensky won the William B. Coley Award in 2015.

—James Allison becomes Chair of Immunology at MSK

Immunologist James Allison joins MSK to help steer the clinical development of a new drug that blocks a molecule on immune cells called CTLA-4. Dr. Allison was the first to show, in 1996, that blocking CTLA-4 could cure cancer in mice. The new drug, called ipilimumab, opens up a whole new approach to cancer treatment geared toward “releasing the brakes” on the immune system. For his research, Dr. Allison won the William B. Coley award in 2005, the Lasker Award in 2015, and, along with Tasuku Honjo, the 2018 Nobel Prize in Medicine or Physiology.

—Ipilimumab FDA approved for treatment of melanoma

Ipilimumab (Yervoy®), an immune checkpoint inhibitor, is approved by the FDA for the treatment of advanced melanoma, based on clinical trials led by Jedd Wolchok. Patients at MSK began receiving ipilimumab in 2004, under the care of Dr. Wolchok. These patients are some of the earliest patients in the world to receive this drug, and a number of them are still alive today.

—Cancer immunotherapy voted “Breakthrough of the Year”

Cancer immunotherapy is voted “Breakthrough of the Year” by Science magazine. Among the promising approaches highlighted by the magazine are checkpoint blockade therapy and CAR T cell therapy — two areas pioneered by MSK scientists.

—Study shows why only some patients respond to immunotherapy

Physician-scientist Timothy Chan and colleagues publish a paper in Science that helps to explain why some people with lung cancer respond better than others to immunotherapies targeting the PD-1 immune checkpoint. Tumors with many genetic mutations seem to generate stronger immune responses than those with fewer. Two PD-1 immunotherapies, pembrolizumab and nivolumab, are now FDA approved for lung cancer.

—FDA approves first-ever immunotherapy combination

A combination of two immunotherapy drugs, ipilimumab and nivolumab, is approved by the FDA for the treatment of advanced melanoma, based on work by cancer immunologist Jedd Wolchok. Dr. Wolchok led the clinical trials that showed improved responses in patients receiving this combination versus ipilimumab alone. Many people believe that immune combinations will enable more patients to benefit from immunotherapy.

—FDA approves immunotherapy for advanced kidney cancer

The PD-1–blocking immunotherapy nivolumab is approved by the FDA for the treatment of advanced renal cell carcinoma, based on results of a large clinical trial led by MSK kidney cancer expert Robert Motzer.

—Parker Institute for Cancer Immunotherapy established

MSK is one of six founding centers of the Parker Institute for Cancer Immunotherapy, established through a $250 million grant from tech entrepreneur and philanthropist Sean Parker. The goal of the Parker Institute is to accelerate breakthroughs and drug development in cancer immunotherapy.