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Unleashing the Immune System to Target Cancer

Dr. Mark Rubinstein
Dr. Mark Rubinstein in his laboratory.

Colleagues John Wrangle, M.D., and Mark Rubinstein, Ph.D., have been working closely on a clinical trial that has now progressed to phase 2b. This clinical trial focuses on an immunotherapy combination that may help patients with non-small cell lung cancer who do not benefit from checkpoint therapy alone.

In the phase 1b portion of the clinical trial, they targeted white blood cells, the immune cells that help control the killing of tumor cells. They combined two drugs, nivolumab, an immune checkpoint drug that essentially cuts the brake cables on white blood cells, and ALT-803, a lymphocyte growth factor that fuels these white blood cells.

Rubinstein says, “This is the first published trial, to our knowledge, that has studied the combination of these two classes of drugs” Wrangle, the national principal investigator for the study, works closely with Rubinstein and his team to analyze tumor and blood samples from the trial.

Dr. John Wrangle
Dr. John Wrangle

Rubinstein says they hope to figure out why some patients are responsive to the drug combination while others aren’t. One of the concerns was that by unleashing the immune system in these two ways, there would be unacceptable toxicity, but they have found that this isn’t the case. Now they have moved on to phase 2b of this clinical trial, which will begin to look at the effectiveness of this treatment.

“I became interested in cancer immunotherapy because I was curious about the science, felt this was an area that was understudied, at the time, and most importantly, that this area of research had real potential to be impactful to help patients.”
- Dr. Mark Rubinstein

The hope is that the combined use of these two therapies will improve the response rate.  “From a research perspective, what is critical to note is that John Wrangle and I are investigating the white blood cells and what happens to them over time.  We want to figure out what changes there are in the white blood cells of patients that have very good responses, and how do we help all patients have the same types of changes.” says Rubinstein.

He hopes that their research in cancer immunology, dealing with lung cancer, will lead to a generalized approach that will work for other types of cancer.

What are Clinical Trials?

Clinical trials explore promising new approaches for cancer prevention, diagnosis and treatment, often providing access to new drugs and interventions before they become widely available. Ask your doctor if a clinical trial is right for you.

Find out more about Hollings’ clinical trials at