Monday, June 6, 2016

Cancer is smart, but your immune system is smarter. That’s why, for more than 120 years, MSK scientists have been fighting cancer with immune cells.


Cancer is smart, but your immune system is smarter.

That’s why, for more than 120 years, MSK scientists have been fighting cancer with immune cells.




At Memorial Sloan Kettering, we believe that immunotherapy is one of the most promising ways to treat, cure, and ultimately prevent cancer.
Immunotherapy was born at MSK more than a century ago. Since then our scientists have led the effort to develop new immune-based treatments for cancer. Our researchers have been at the epicenter of new discoveries in the field, and their work is bringing exciting new treatment options to people with cancer. 
Patients who come to MSK for immunotherapy treatment benefit from unparalleled expertise in a field that our scientists pioneered.   
Cancer immunologists Marchel van den Brink & Jedd Wolchok
Marcel van den Brink (left) and Jedd Wolchok lead the Parker Institute for Cancer Immunotherapy at MSK.
[TOP] Discoveries made in the lab of Immunology Program Chair Alexander Rudensky have changed the field of immunology. [BOTTOM] CAR T cell therapy pioneers: (from left) Isabelle RivièreMichel Sadelain, and Renier Brentjens.
How We Care for Patients
  • Our immunotherapy patients benefit from the close collaboration between our doctors and scientists.
  • Discoveries in the lab are constantly being translated into new therapies for patients.
  • We’re currently running nearly 100 immunotherapy-focused clinical trials.
  • Our experts are seeking out new ways to help the immune system recover after a bone marrow transplant.
  • Our science has already begun to change how melanomaleukemia, and lungbladder, and kidney cancers are treated.
MSK is home to a diverse group of scientists who study the immune system in all its complexity. Our laboratory scientists include many immunologists, geneticists, and cell biologists who explore the biology of immune cells and their interactions with tumors and infectious organisms.  
Our physician-scientists are developing groundbreaking immune therapies that are helping to treat several forms of advanced cancer. They have played a lead role in developing and testing the immunotherapy drugs known ascheckpoint inhibitors that “release the brakes” on the immune system, allowing it to mount a stronger attack against cancer. These drugs are transforming the way many cancers are treated, among them melanoma, lung, bladder, and kidney cancers.
MSK scientists have also led the way in using chimeric antigen receptor (CAR) T cell therapy to treat leukemia and certain solid tumors. In this approach, immune cells from a patient are removed from the body, armed with new proteins that recognize cancer, and given back to the patient in large numbers. 
MSK is a leader as well in bone marrow transplantation for children and adults with blood cancers such as leukemia.

Where Immunotherapy Began

Memorial Sloan Kettering’s roots in immunotherapy extend all the way back to 1893, when bone surgeon and cancer researcher William Coley began his work here on bacterial vaccines. 
In the decades that followed, MSK scientists put cancer immunotherapy on firm scientific footing. Their many discoveries have helped make immunotherapy what it is today.
View our timeline of progress to see how MSK scientists have been at the forefront of immunotherapy research for more than 120 years.
William Coley (center) (Source: Cancer Research Institute)

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.”
Lewis Thomas

1957

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. 
Charlotte Friend (Source: Mount Sinai archives)

1957

Leukemia virus discovered

Virologist Charlotte Friend, while working at theSloan 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.
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1959

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.” 
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1966

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.
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1968

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.
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1973

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.
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1975

Cancer-killing immune molecule discovered

Lloyd Old, Elizabeth Carswell, and colleagues identifytumor 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.
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1982

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.
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1990

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.
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1997

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.
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2001

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.   
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2002

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.
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2003

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. 
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2004

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 and the Lasker Award in 2015.
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2011

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 clincal 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. 
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2013

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.
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2015

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.
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2015

Study shows why only some patients respond to immunotherapy

Medical oncologist Matthew Hellmann and radiation oncologist Timothy Chan co-author a paper inScience 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.   
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2015

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.
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2016

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.
 
1957

Cancer immunosurveillance hypothesis proposed

Leukemia virus discovered

Studies of BCG launch modern era of tumor immunology

Viral cause of nasopharyngeal cancer uncovered

First successful bone marrow transplant from a sibling performed

First bone marrow transplant from an unrelated donor performed

Cancer-killing immune molecule discovered

Cancer antigens identified in melanoma

BCG immunotherapy approved by the FDA

New cancer-associated antigen identified

Treatment developed to enhance immune recovery

Chimeric antigen receptor (CAR) T cells developed

Genetic switch for regulatory T cells discovered

James Allison becomes Chair of Immunology at MSK

Ipilimumab FDA approved for treatment of melanoma

Cancer immunotherapy voted “Breakthrough of the Year”

FDA approves first-ever immunotherapy combination

Study shows why only some patients respond to immunotherapy

FDA approves immunotherapy for advanced kidney cancer

Parker Institute for Cancer Immunotherapy established

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Parker Institute for Cancer Immunotherapy

Immunity science at MSK spans one academic program and four collaborative research centers, including our newest center, the Parker Institute for Cancer ImmunotherapyThe Parker Institute, established by tech entrepreneur Sean Parker, brings together top researchers in the field from Memorial Sloan Kettering and five other founding partner institutions, with the aim of speeding the discovery and development of new immunotherapy treatment options.
MSK’s Parker Institute members are dreaming big — pursuing projects that will not only improve existing immunotherapies but also open the door to new ones. The support offered through the Parker Institute will allow them to build on MSK’s leadership as we search for new ways to extend the benefits of immunotherapy to even more patients.
Immunotherapy is the disruptive technology of cancer medicine.
Jedd D. Wolchok
Jedd D. WolchokLloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation; Chief, Melanoma & Immunotherapeutics Service; Associate Director, Ludwig Center for Cancer Immunotherapy
Parker Institute Director Jedd Wolchok has played a central role in developing and testing the immunotherapy drugs known as checkpoint inhibitors. He led pivotal clinical trials leading to the FDA approval of ipilimumab, the first immune checkpoint inhibitor, for advanced melanoma in 2011. He also led studies leading to the FDA approval of the first-ever immunotherapy combination for people with advanced melanoma.
Co-Director Marcel van den Brink is a world-renowned expert on cell-based immunotherapy and bone marrow transplantation, approaches that are successfully treating and in some cases curing several types of blood cancer. His work has led to novel therapeutic strategies for graft-versus-host disease and immune reconstitution after bone marrow transplantation.

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