On the Immunotherapy Frontier

  • Published: October 26, 2016

How did Dr. Jim Allison, renowned researcher, member of the Parker Institute for Immunotherapy and winner of the 2015 Lasker Award wind up as the Chairman of Immunology at The University of Texas MD Anderson Cancer Center?

The answer is CPRIT.

In November 2011, Dr. Allison was recruited back home to Texas with the help of a CPRIT grant of $10 million. A native of Alice, Texas and the son of a country doctor, Allison returned to Texas from Memorial Sloan-Kettering in New York to advance his groundbreaking research into checkpoint inhibitors, and translate that into drugs made of antibodies capable of unleashing a body’s immune system to attack cancer cells.

Dr. Allison now leads the immunology department at MD Anderson Cancer Center. There, he has established the cancer immunotherapy platform, a combination of talented research associates and laboratory infrastructure working together to better understand and advance cancer immunotherapy and translating basic research to the bedside.

Without question, immunotherapies have opened up entirely new lines of activity and thinking in cancer research. Patients’ immune systems can be inhibited from attacking cancer cells, a condition that allows cancers to grow and spread, but this is where Allison’s work has made the biggest difference. He found a protein, CTLA-4, and proved that it behaves like a brake on immune responses. Most scientists at the time believed CTLA-4 amplified people’s immune system. That discovery was translated initially into the drug Yervoy, which removes the brake allowing the immune system to find and attack cancer cells.

“Dr. Allison not only had the insight to invert the assumptions on CLTA-4, but he had the persistence to push it into drug development,” said Dr. James Willson, oncologist and CPRIT Chief Scientific Officer. “He literally proved that the immune system could indeed be harnessed to fight cancer and now many other scientists are joining him on this frontier. It’s tremendously exciting.”

In addition to checkpoint inhibitor advancements, the immunotherapy frontier is being pushed forward by three other immunotherapies: monoclonal antibody therapies, cell therapies using natural killer cells and Chimeric Antigen Receptor T-cell (CAR-T) therapies. These strategies are being evaluated in patients with cancer by manipulating cells to strengthen or suppress their immune functions, depending on their unique cancer type. In CAR-T cell therapy, for example, strengthening cell function includes helping cells better recognize and destroy cancer cells.

Willson went on to tick off a short list of the CPRIT scholars at work in each of the immunotherapy fronts:

Checkpoint Inhibitors

Dr. Jennifer Wargo, MD Anderson – Wargo is analyzing biopsies in patients with melanoma and other cancers on targeted therapy and immunotherapy to better understand their responses to the treatment.

Cell and CAR-T Therapy

Dr. Cassian Yee, MD Anderson – Dr. Yee is seeking to develop adoptive T cell therapy as a clinically feasible treatment modality for patients with solid tumor malignancies in general.

Dr. Andrew Futreal, MD Anderson – Futreal is aiming to accelerate the translation of genomic technologies in therapeutic applications.

Dr. Yang-Xin Fu, UT Southwestern Medical Center – Dr. Yang researches how traditional cancer therapies rely on and impact the immune system of a patient.

Dr. Leonid Metelitsa, Texas Children’s Hospital - Metelitsa’s work was supported by a CPRIT product development grant to the company Cell Medica.

Monoclonal Antibodies

Dr. E. Sally Ward, Texas A&M University – Dr. Ward is taking a highly interdisciplinary approach to generate effective therapeutics for autoimmunity and cancer.

The results being reported by these researchers are encouraging and exciting. Up to 20 percent of patients involved in clinical trials for certain types of cancers, for example, melanoma and lymphoma are actually being cured by checkpoint inhibitor drugs. On-going clinical trials using gene and cell based approaches are showing promise in patients with a variety of different types of cancer including cancers of the colon, kidney, ovaries, pancreas and prostate.

“Texas is on the leading edge of immunotherapy discovery,” said Willson. “We have been building the armamentaria and now, some of the most exciting work in the field is happening in our state. CPRIT funding is at the heart of it.”

Immunotherapy is funded by CPRIT through its Research program and its Product Development program. To date, total CRPIT funding for basic, translational and clinical research has been $780,642,003 while $296,558,359 has been directed by CPRIT toward product development through companies such as Bellicum, Immatics US Inc. and Cell Medica.

More CPRIT Stories: Cancer Prevention & Research Institute of Texas Awards 14 New Grants