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June 1, 2018
Mellman Optimistic About Cancer Immunotherapy

Dr. Ira Mellman, vice president for cancer immunology at Genentech, Inc., had just come back from the American Association for Cancer Research annual meeting in Chicago when he gave a Wednesday Afternoon Lecture Apr. 18 in Masur Auditorium.

Dr. Ira Mellman of Genentech is optimistic about cancer immunotherapy and immunology.
Dr. Ira Mellman of Genentech is optimistic about cancer immunotherapy and immunology.

PHOTOS: MARLEEN VAN DEN NESTE

“There is a great deal of excitement due to recent work in cancer immunology and immunotherapy,” he reported. “The field had been in the depths of despair for years. Now everybody wants to get in on the act, which is terrific, because it’s a very good act to be in.”

Mellman is principally interested in “what we can do for patients by modulating the immune system, and what we can learn about cancer immunity by studying patient response.”

He and his colleagues have identified what they call the cancer immunity cycle, which has two phases: activation and effector.

His company has created an anti-PD-L1 antibody that, while not completely understood, targets the effector side of the cycle and has proven effective across a broad range of tumors, but in only 10-30 percent of patients. It is approved for both bladder and non-small-cell lung cancer.

Mellman said the antibody, atezolizumab, confers a good survival benefit for all second line non-small-cell lung cancer patients, but the benefit is particularly large in those individuals whose tumors express the PD-L1 protein itself.

“The PD-L1 diagnostic is a valuable and interesting tool, one that has taught us a lot,” he said. “But it is not a perfect biomarker, as some PD-L1-negative patients derive benefit from therapy while some PD-L1-positive patients fail to benefit.”

Dr. Ira Mellman

He and his collaborators continue to search for drug targets of immunotherapy and are now trying combinations of two inhibitors in a phase 3 trial that will read out this spring.

In his talk, Mellman also touted immunotherapy results emerging from NCI’s Surgery Branch headed by Dr. Steve Rosenberg, which he called “spectacular.” Mellman is now collaborating with the German company BioNTech to make personalized cancer vaccines.

“Each person will need his or her own vaccine,” he said. Physicians would biopsy a patient’s tumor, identify signature mutations and then craft RNA-liposome complexes that can be delivered intravenously—all in 4 weeks.

“Trials in combination with atezolizumab are under way and we are excited because initial results with vaccine alone (recently published in Nature) appear to have arrested disease recurrence in melanoma patients.”

Mellman added that “in principle, all cancer patients could get their own cancer vaccine…We are just at the beginning stages of the field of determining what immunological factors are most important.”

Mellman’s lecture on “Mechanistic Basis of Cancer Immunotherapy” is available (to HHS employees only) at https://videocast.nih.gov/summary.asp?Live=27208&bhcp=1. —Rich McManus

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