Discoveries in T cell biology, development of immune checkpoint blockade cancer therapy honored
Basic science research that exposed vital details of cancer's defense against the immune system, revealing an entirely new way to combat these diseases, has earned Jim Allison, Ph.D., a Breakthrough Prize in Life Sciences.
Allison, chair of The University of Texas MD Anderson Cancer Center's Immunology department and executive director of the Moon Shots Program immunotherapy platform, received the $3 million honor at a ceremony in San Francisco Thursday night.
Entrepreneurs Sergey Brin and Anne Wojcicki, Jack Ma and Cathy Zhang, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan, sponsor the prize to recognize excellence in research aimed at curing intractable diseases and extending human life.
"Scientists should be celebrated as heroes, and we're honored to be part of today's celebration of the newest winners of the Breakthrough Prize in Life Sciences and the Fundamental Physics Prize," said Anne Wojcicki and Sergey Brin in a news release announcing the awards.
"I'm honored and exhilarated to receive this generous award established by the founders of the Breakthrough Prize in Life Sciences Foundation," Allison said. "My profound thanks go to them for recognizing my own work and for establishing this prize to promote research, celebrate scientists and to generate excitement about careers in science."
Among the uses for the prize funds that Allison is considering is a program for high school students and college undergraduates to foster their interest in biomedicine.
Growing up in Alice, Texas, Allison's own interest in science was cultivated and encouraged by summer programs at The University of Texas at Austin where he attended starting in middle school.
"Real hope for cancer patients around the world"
"Jim Allison richly deserves this wonderful prize for his pioneering research into how tumors evade destruction by immune system attack and how to overcome that defense by treating the immune system, rather than the cancer directly," said MD Anderson President Ronald DePinho, M.D. "I extend my deepest appreciation to the Breakthrough Prize selection committee and its visionary sponsors for their recognition of Jim's work that has offered real hope for cancer patients around the world."
Allison's research on the biology of T cells, immune system attack cells primed to identify and destroy infections and the body's abnormal cells, has led to several discoveries:
Identification of the receptor on T cells used to recognize and bind to antigens - abnormalities that mark defective cells or viruses and bacteria for attack.
The discovery that T cells require a second molecular signal from co-stimulatory molecules to launch a response after they've bound to an antigen.
A discovery involving a receptor on T cells called CTLA-4 that acts as a built-in off switch to stop T cells from attacking. These immune checkpoints usually protect normal tissues from autoimmunity and aren't effective on abnormal cells. Cancer cells, however, activate CTLA-4.
Allison then developed an antibody that led to development of ipilimumab to block CTLA-4. In clinical trials against stage 4 melanoma, the drug extinguished the disease in 24 percent of patients for up to 12 years and counting, unprecedented results against metastatic melanoma. The drug, now called Yervoy, was approved to treat melanoma by the U.S. Food and Drug Administration in 2011.
Checkpoint blockade at work in many cancers
This work stimulated discovery of additional immune checkpoints and development of experimental drugs to block them. Clinical trials of ipilimumab and other agents are under way at MD Anderson and elsewhere are demonstrating effectiveness against a variety of other cancers.