Many critics of spending billions of dollars on cancer research typically point to the fact that a general cure for neoplastic diseases had not been discovered (see: “After Spending Billions, Why have Scientists Not Yet Found a Cure for Cancer?” ). That now is no longer a convincing question, thanks to the basic and applied research of James P. Allison, PhD (University of Texas M. D. Anderson Cancer Center, in Houston). His breakthrough experiments and new ideas for anticancer therapy led to remissions and probable cures for some cancer patients who previously had no hope. This article briefly describes Dr. Allison’s research on the functioning of specialized cells in the immune system, which led to discovery of a very new effective approach for therapeutic treatment of cancer.
The Lasker Awards.
Each year, the Albert and Mary Lasker Foundation  bestows 3 Lasker Awards: Albert Lasker Basic Medical Research Award, Lasker-DeBakey Clinical Medical Research Award, and, Lasker-Bloomberg Public Service Award. The 2015 Lasker Awards and Laureates all are nicely described on the Foundation website: http://www.laskerfoundation.org/media/index.htm . Lasker Awards are considered to be most prestigious for medical science, and the awardees often are considered to be likely to soon receive a Nobel Prize.
Dr. Allison has just won the very prestigious Lasker-DeBakey Clinical Medical Research Award for 2015 for his innovative new immunotherapy against cancer [2-4]. He previously has received numerous other honorary awards, including the 2014 Breakthrough Prize in Life Sciences  and the 2014 Szent-Györgyi Prize from the National Foundation for Cancer Research .
A new kind of anti-cancer immunotherapy is developed by Dr. Allison [2-6]!
Many different immunology-based therapies against cancer have been investigated, but most have produced only limited clinical benefits. The experimental treatment of cancer with antibodies that specifically bind to molecular components produced by cancer cells has not been successful. Dr. Allison’s early research investigated the molecular mechanisms for how some cells of the immune system, T-cells, work in the cellular immune response to recognize and kill bacteria, viruses, and abnormal cells in the body. T-cell activities are nominally independent from antibody responses of the immune system.
Detailed research about T-cell surface receptors, binders, and cofactors led to Dr. Allison’s recognition that there are both positive on-signals and negative off-signals regulating T-cells. One of the down-regulators is a receptor protein named, CTLA-4; upon binding of CTLA-4 to it’s targets, the activation and proliferation of T-cells are turned off. This negative regulation is normal and is believed to prevent active T-cells from attacking the body’s own constituents (i.e., autoimmune diseases).
Most immunologists have long thought that the immune system should recognize, attack, and kill cancer cells. Thus, it was a mystery why such does not happen. This puzzle led Dr. Allison to ask whether CTLA-4 might be turning off a T-cell response against cancer cells. He tested this hypothesis by developing antibodies that specifically bind CTLA-4 molecules, thereby inactivating their functional activities, including the down-regulation of T-cells. When these antibodies were injected into laboratory mice bearing a transplantable tumor, there was a large proliferation of T-cells and strong killing of cancer cells inside the tumors! Injecting control antibodies which bound other proteins had no effects on T-cells, so the tumor-bearing mice died. Thus, these and other experimental results showed that stopping the normal down-regulation of T-cells released them to give a strong response against neoplastic cells. The brakes on T-cells had been released by Dr. Allison, so their endogenous anti-cancer activities now went full speed ahead! The go/no-go interaction between CTLA-4 and T-cells now is known as an immune checkpoint.
The next step in this ongoing research project involved translating the findings from basic research into applied clinical research with experimental treatment of human cancer patients. After finally finding a pharmaceutical company willing to collaborate with production and testing of anti-CTLA-4 human antibodies, Dr. Allison began initial clinical trials of this experimental treatment of cancer patients who had not responded to any usual surgical, chemical, or radiation therapy. In some cases the new immunotherapy worked quite well! A standardized commercial version of human anti-CTLA-4 antibodies was approved for clinical use in 2011; over 30,000 cancer patients now have received the new immunotherapy. This new cancer treatment is not just another promise of some hoped for future development; it is here today, and actually saves the life of some cancer patients.
Ongoing research in anti-cancer immunotherapy by Dr. Allison and other scientists [2-6].
The door now was opened to try this very new kind of anti-cancer therapy with different patients, different cancers, and different therapeutic protocols. The effects of anti-CTLA-4 antibodies had dramatic results for some patients with malignant myeloma, a blood cell cancer that usually is fatal within one year. The anti-CTLA-4 therapy put some, but not all, myeloma patients into long-term remission (i.e., over 14 years)! New research, both by Dr. Allison and by other clinical research scientists, seeks to find: (1) why some malignant myeloma patients do not respond to this new therapy, (2) which additional cancers can be treated by this immunotherapy, (3) whether manipulating other proteins regulating T-cell activities will provide additional curative effects, (4) will combination treatments of cancers (e.g., immunotherapy with concurrent chemotherapy) give even better curative effects, and, (5) can manipulating other immune checkpoints have therapeutic effects against any non-cancer diseases?
Special features of this very new kind of immunotherapy.
Some distinctive very special features of this new kind of immunotherapy must be recognized by all readers!
(1) The new curative therapy is targeted against the immune system, and not against cancer cells.
(2) T-cells can effectively kill cancer cells; thus, an endogenous response is what kills the cancer cells.
(3) Endogenous activities of T-cells against neoplastic cells normally are halted by activities of CTLA-4.
(4) Right now, this new immunotherapy probably cures several types of cancer in some patients.
Dr. James Allison deserves immense credit for coming up with new ideas and new research findings about the immune system, and for asking new clinical questions. He is an superb example of how PhD scientists investigating pure basic science in a laboratory can contribute much to applied clinical research. Individual scientists having creativity, curiosity, enthusiasm, and the guts to think new thoughts, just like Dr. Allison, are the best hope for more important discoveries in all branches of scientific research.
Dr. Allison very clearly has made a wonderful contribution to modern clinical medicine. All of us can hope that additional cancers finally will be conquered with the results from further research studies and innovative medical developments. In addition, new approaches to immunotherapy might also benefit patients with some non-cancer diseases.
Recommended videos by and about Dr. James Allison!
“James Allison’s Cancer Research Breakthrough”, 2014, is available at: http://www.youtube.com/watch?v=ySG2AwpSZmw&spfreload=10 .
“Dr. Jim Allison – 2014 Szent-Györgyi Prize”, 2014, is available on the internet at: http://www.youtube.com/watch?v=YGu2uzV9QOM .
“James P. Allison, Ph.D. on Targeting Immune Checkpoints in Cancer Therapy”, 2015, is available at: http://www.youtube.com/watch?v=CoBkuTOPJqg .
 Lasker Foundation, 2015a. Foundation overview. Available on the internet at: http://www.laskerfoundation.org/about/index.htm.
 Lasker Foundation, 2015b. Lasker-DeBakey Clinical Medical Research Award. Award description. Available on the internet at: http://www.laskerfoundation.org/award/2015_c_description.htm .
 Lasker Foundation, 2015c. Lasker-DeBakey Clinical Medical Research Award. Award presentation by Michael Bishop. Available on the internet at: http://www.laskerfoundation.org/awards/2015_c_presentation.htm .
 University of Texas M. D. Anderson Cancer Center, Newsroom, 2015. MD Anderson immunologist Jim Allison wins Lasker-DeBakey Award. Available on the internet at: http://www.mdanderson.org/newsroom/news-releases/2015/allison-wins-lasker-award.html .
 University of Texas M. D. Anderson Cancer Center, Newsroom, 2013. M.D. Anderson researcher Jim Allison wins Breakthrough Prize for his innovative cancer immunology research. Available on the internet at: http://www.mdanderson.org/newsroom/news-releases/2013/immunology-research.html .
 National Foundation for Cancer Research, 2015. The Szent-Györgyi Prize for progress in cancer research. Available on the internet at: http://www.nfcr.org/prize .
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