Fighting Cancer

"This is a fundamental change in the way that we think about cancer therapy."
Dr. Jedd Wolchok, chief of melanoma and immunotherapeutics services, Memorial Sloan Kettering, New York

"We can say in all honesty to patients, that while we can't tell them we can cure metastatic lung cancer right now, we can tell them there's real hope that they can live for years, and for a lot of patients many years, which really is a complete game-changer."
Dr. John C. Heymach, chairman, thoracic/head and neck medical oncology, M.D. Anderson

"I became interested in cancer because I've lost a number of family members to cancer."
"My mother and two of her brothers, and my own brother, died of cancer."
Dr. James P. Allison, chairman, immunology department; executive director, immuno-therapy platform, M.D. Anderson Cancer Center, University of Texas

"It's like buying a lottery ticket. The more genetic abnormalities, the more lottery tickets  you've bought -- and you have a much higher chance of a T-cell recognizing something to start the immune response."
Dr. Padmanee Sharma, professor of genitourinary medical oncology, M.D. Anderson Cancer Center, Houston, Texas

M.D. Anderson Cancer Center

Dr. Allison together with a colleague Dr. Jeffrey Bluestone of the University of California at San Francisco made an important discovery in the 1990s. They found a molecule whose function was believed to activate the immune system, in fact quite the opposite, shut it down. This was a protein positioned on the surface of T-cells, evidently nature's plan to subdue T-cells to ensure they would not attack a body's own tissue, rather than foreign tissue.

Cancer cells are known to occasionally lock onto checkpoints, which is what this molecule is, to disable the T-cells. The body's immune system sometimes goes awry; it is suspected by medical science that Type I (juvenile) diabetes is caused by the body's immune system mistakenly attacking the body's Beta cells in the Islets of Langerhans to destroy the insulin-producing capabilities of the cells, causing diabetes onset, as an example.

It occurred to Dr. Allison to wonder whether blocking the checkpoint to launch T-cells against cancer might be conceivable. So, together, he and a postdoctoral fellow Dana Leach, developed a molecule produced by certain cells of the immune system, as an antibody to stick to the checkpoint to block it. When laboratory mice were given the antibody their cancer tumours vanished, amazing Dr. Allison by the positive response to his theory.

A human version of the antibody is now produced by Bristol-Myers Squibb with the trade name Yervoy, approved to treat advanced melanoma, becoming the first drug to prolong survival in those with this usually-deadly cancer. Before the drug was approved, studies concluded that among 1,861 patients who received treatment for the advanced disease, roughly 22 percent remained symptom-free after three years.

Immunotherapy is an entirely new class of cancer treatment with unique characteristics that differentiate it from other kinds of cancer therapies.

Immunotherapy is an entirely new class of cancer treatment, with unique characteristics that differentiate it from other kinds of cancer therapies. - See more at: http://www.cancerresearch.org/cancer-immunotherapy#sthash.qaf2BUp1.dpuf

Immunotherapy stands to revolutionize the treatment of almost every kind of cancer.
- See more at: http://www.cancerresearch.org/cancer-immunotherapy#sthash.qaf2BUp1.dpuf

Dr. Allison, a researcher who has up to now won numerous awards in recognition of his work, may in the near future become a Noble Laureate. Dr. Allison's and his wife Dr. Sharma's research focus is to achieve the understanding of how and why checkpoint inhibitors work in some patients and fail to in other patients. Seeming to work most effectively for tumours with a multitude of mutations, like most melanomas and cancers of the lung and bladder.

In 2011, the U.S. Food and Drug Administration approved immunotherapy drugs. One protocol represents an individualized treatment geared to each patient where some of the individual's immune cells are removed to genetically alter them to kill cancer when they are infused back into the bloodstream. Long remissions in a few hundred children and adults with deadly forms of leukemia or lymphoma has resulted.

Another approach, the second of the two, involves mass-produced drugs that are generic in nature, not tailored to each patient, where the drugs free immune cells to battle cancer through blocking the checkpoint mechanism used by cancer cells to shut down the immune system. This protocol is used in the treatment of advanced melanoma, Hodgkins's lymphoma and cancers of the lung, kidney and bladder.

One of the drugs, Keytruda, was used to treat former U.S. President Jimmy Carter's advanced cancer. Combined with surgery and radiation the use of the drug left the former president with no symptoms of recurrence despite the fact that melanoma had spread to his liver and his brain. His success story has acted as a spur to the patient community eager to have similar outcomes for themselves, begging to be placed in trials.

But the other part of the story is that up to now, immunotherapy has succeeded for only a subset of patients, the majority have not responded to the promise of immunotherapy and the reasons elude researchers. There is great trust and belief in the potential of immunotherapy, but these results where only a minority of patients respond well to their use, is a puzzle that must be solved. As Dr. Sharma said, "It's like buying a lottery ticket".

Immunotherapy

Immunotherapy is a type of biological therapy that uses the immune system to help destroy cancer cells. Immunotherapy may be active or passive.

• Active immunotherapy stimulates and strengthens the body’s immune system response so that it attacks and destroys cancer cells. It can be either non-specific or specific.
  • Non-specific active immunotherapies (such as interferon and interleukin) stimulate or boost the immune system in a very general way.
  • Specific active immunotherapies (such as cancer vaccines) use antigens of a specific type of cancer cell to trigger an immune response. They do not cause a general immune system response.
• Passive immunotherapy uses substances that act like parts of the immune system and attack specific cells. These substances are made in a laboratory. Treatment using monoclonal antibodies is an example of passive immunotherapy.