ClinicalResearch
When USC Norris Comprehensive Cancer Center member Ann Mohrbacher, MD, began her career in immunology, the idea that physicians one day could fight cancer using the body’s own immune system was still science fiction. Research at the time was focused on lupus, an autoimmune disease, rather than cancerous diseases like lymphomas — until researchers found that the immune system also can be directed to control cancer cells.

“I was one of the early investigators with Rituximab, the very first designed immunotherapy for cancer,” says Mohrbacher, medical director of the Autologous Bone Marrow Transplant Program in the Blood Diseases Center at USC Norris. “I remember one of my colleagues saying, ‘Oh my gosh, do you really think we’re going to treat cancer with an antibody?’”

Mohrbacher, an associate professor of clinical medicine in the Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, says that once the trial showed results, it changed the way researchers looked at cancer research. “That turned out to be the most amazing drug of two decades and totally broke barriers — the first immunotherapy to successfully fight cancer,” she says. By using the body’s immune system to target cancer cells, physicians are learning how to treat patients who may not be responding to chemotherapy. Since those early days in research, Mohrbacher has continued her work in immunotherapy alongside colleagues in the Blood Diseases Center at USC Norris, where researchers are bringing leading-edge technology to the treatment and study of diseases of the blood.

Another approach to activating the body’s own immune system to control cancer is by using viruses as a cancer treatment. A study that is being led by Kevin Kelly, MD, PhD, an associate professor of medicine in the Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, is examining the use of a form of the human reovisrus (Reolysin), a naturally occurring virus that preferentially targets and destroys cancer cells.

“Reolysin is being given in combination with standard myeloma treatments,” Kelly says. “The objective is to determine the safety and effectiveness of the virus in combination with the standard chemotherapy in myeloma. We are studying the myeloma cells of each patient that is enrolled to identify the patients that will respond preferentially to the virus. We also are determining if Reolysin can re-educate the immune system to target and destroy myeloma.”

By re-educating the immune system, physicians may be able to help patients who are no longer responding to standard treatment. “The trial is based on exciting research in the lab that shows that myeloma cells have high levels of the receptor for the virus,” Kelly says. “We noticed that myeloma cells had a very high expression of receptors for the virus and in particular myeloma patients who had relapsed after standard treatment had an even higher expression of the Reolysin receptor. The Reolysin receptor may be an Achilles heel in the drug-resistant myeloma cell that we can take advantage of.”

The study is one of several ongoing clinical trials that are looking to the future of cancer research. With lessons learned in clinical trials for combined immunotherapies and viral therapies, physicians may be able to move away from using chemotherapy for longterm remission and focus on using the body’s immune system to deliver cancer-killing drugs. Those clinical trials and the patients participating in them are crucial to advancing the understanding of cancer and improving its treatment.

“In the end, we have to thank the patients who are brave enough to try a new treatment,” notes Mohrbacher. “The courage of the patients to participate is what finally makes it all move forward.”

For more information about clinical trials at USC Norris Comprehensive Cancer Center, visit clinicaltrials.keckmedicine.org. To support research at USC Norris, please call (323) 865-0700 or email norrisdev@usc.edu.

by Melissa Masatani