Cancer Pioneer James Allison Leads MD Anderson Immunotherapy Efforts

Drug from scientist’s research helps the immune system recognize and destroy malignant cells

MD Anderson News Release 11/2/2012

James Allison, Ph.D., whose groundbreaking research is stripping away cancer’s ability to evade attack by the immune system, is the new chair of The University of Texas MD Anderson Cancer Center Department of Immunology.

Watch video on how Allison brings immunotherapy expertise to MD Anderson. 

“Jim Allison’s discoveries led to the first drug ever to improve the survival rate of patients with metastatic melanoma – by itself a remarkable achievement. His insights into the basic biology of immune system T cells will be broadly applicable to a variety of cancers and his gifted scientific leadership is essential to the definitive progress that must be made against these diseases,” said MD Anderson President Ronald DePinho, M.D.

“We’re delighted that he will lead our collaborative immunotherapy initiative to continue unleashing the power of the immune system against cancer,” DePinho said. “Dr. Allison embodies an important principle for us. It’s not just about doing elegant science, although that’s certainly the case here. It doesn’t count unless it has a meaningful impact on the well-being of our patients. That’s the bottom line.”

Accelerating transition of drug combinations to clinic
“The main reason for coming to MD Anderson is the opportunity offered by a clinical community that’s open to using immunological approaches to treat cancer combined with other therapies,” Allison said.

“We plan to build a large platform where basic scientists interested in mouse models of cancer work side-by-side with physician-scientists who treat patients to analyze tissues from those patients and truly understand the mechanisms involved,” Allison said. “We can accelerate the transition of new combinations of drugs into the clinic beyond phase I clinical trials and broaden our focus beyond melanoma and prostate cancer to other types of cancer.

“We all know that no single drug will cure cancer. I think this is where we’ll start getting cures, or at least long-term survival of patients. There’s lots of enthusiasm for this approach at MD Anderson and I’m really excited about it,” he said.

Allison will play an instrumental role in MD Anderson’s recently announced Moon Shots Program to dramatically accelerate the pace of converting scientific discoveries into clinical advances that reduce cancer deaths.

He is a member of the National Academy of Sciences and the Institute of Medicine, as well as a fellow of the American Academy of Microbiology and the American Association for the Advancement of Science. He also is an investigator of the Howard Hughes Medical Institute.

Allison was chair of the immunology program and director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center in New York.He started at MD Anderson on Nov. 1.

Immune system personalizes therapy
Rather than attacking cancer cells directly, the drug developed from Allison’s research makes those cells “visible” to the immune system by blocking a molecule he discovered that inhibits immune response.

About 25 percent of patients with late stage metastatic melanoma who took ipilimumab in clinical trials have lived for five years or longer. The drug, known commercially as Yervoy, was approved by the U.S. Food and Drug Administration in May 2011.

In addition to recognizing invaders such as bacteria and viruses, the immune system also identifies and destroys genetically abnormal cells, proteins and bits of proteins called peptides.

Genomic instability is a hallmark of cancer cells so they should be prime targets for the immune system, Allison said. Cancer cells evade this attack, and Allison’s T cell discoveries provide insight into why.

T cells are lymphocytes, a type of white blood cell produced by the thymus equipped with receptors that recognize and bind to antigens – distinctive pieces of invading organisms, abnormal cells or proteins, captured and presented to the T cells by antigen-presenting cells. T cells launch customized immune responses to destroy these targets.

Allison’s seminal scientific discoveries include:

• The T cell antigen receptor used by T cells to bind to and recognize antigens.
• T cells require a second signal to launch a response after they’ve bound to an antigen. B7 molecules on presenting cells must engage a surface molecule called CD28 on the T cell.
• An immune-inhibiting molecule called CTLA-4 inhibits activated T cells to protect normal tissue from attack.  CTLA-4 apparently also protects cancer cells from attack.

Ipilimumab blocks CTLA-4, which allows the immune system, over time, to recognize and attack cancer cells. This new approach is called immune checkpoint blockade.

Combining targeted therapy with checkpoint blockade can turn cancer’s genomic instability, which it uses to build resistance to drugs, against it, Allison said.

“The idea here is when you kill tumor cells with the targeted drug you cause inflammatory cell death, which introduces lots of new antigens into the system. Combine checkpoint blockade with the drug and you reveal those antigens as targets (for the immune system) and, in effect, turn one drug into many drugs,” Allison explained.

A return to MD Anderson
A native of Alice, Texas, Allison earned his bachelor’s degree in microbiology and his doctorate in biological sciences from The University of Texas at Austin. After his postdoctoral fellowship at Scripps Clinic and Research Foundation in California, Allison’s first faculty appointment was at MD Anderson’s Science Park – Research Division in Smithville, Texas, for eight years.

Allison next moved to the University of California, Berkeley, where he was a professor in the Division of Immunology and director of the Cancer Research Laboratory. He moved to Memorial Sloan-Kettering in 2004.

Allison comes to MD Anderson with the help of a $10 million scientific recruitment grant for established investigators by the Cancer Prevention and Research Institute of Texas.