Novel treatment exposes melanoma to immune system attack


 

Antibodies that lower cancer's guard against an immune system attack caused melanoma growths to recede or stabilize in half of patients who took part in a clinical trial of the therapy, Dana-Farber Cancer Institute scientists will report at the annual meeting of the American Society of Clinical Oncology (ASCO) June 1-5 in Chicago.

The phase I trial involved 104 patients with advanced melanoma, a skin cancer that can become lethal if it spreads to other parts of the body. The patients were treated with a monoclonal antibody — a preparation of millions of identical proteins — that rescinds a "Halt!" order on T cells' attack on melanoma cells.

The antibody targets a receptor called PD-1 on the surface of T cells. In doing so, it targets the interaction between PD-1 and a companion protein, or ligand, called PD-L1. The interaction of PD-1/PD-L1 shuts down T cells' attack on melanoma; blocking that interaction allows the attack to resume.

Stephen Hodi, MDF. Stephen Hodi, MD

"The interaction of PD-1 and PD-L1 essentially stiff-arms the immune system from attacking melanoma," says the lead author of the ASCO study, F. Stephen Hodi, MD, director of the Center for Melanoma Oncology at Dana-Farber. "Blocking that interaction allows the immune system to proceed with the attack. It lets the T cells do their job."

Hodi will present the data (abstract 8507) in an oral session on Monday, June 4, 8 a.m. CT, in the Arie Crown Theater, McCormick Place. Hodi also has provided video commentary on the findings.

Patients participating in the trial received the antibody preparation, known as BMS-936558, for up to two years. Side effects were for the most part minor.

Although the phase I trial is now closed, researchers hope to begin phase II and III studies of the approach later this year.

The research builds on earlier work by Dana-Farber's Gordon Freeman, PhD, and others who identified the PD-L1 ligand on tumor cells and showed how the interaction between PD-1 and PD-L1 can turn off the immune response to cancer. Freeman and his colleagues were also the first to show how monoclonal antibodies could be used to reactivate the immune response.

In addition to Hodi, the study's other authors are Mario Sznol, MD, Yale Cancer Center, New Haven, CT; David F. McDermott, MD, Beth Israel Deaconess Medical Center, Boston; Richard D. Carvajal, MD, Memorial Sloan-Kettering Cancer Center, New York; Donald P. Lawrence, MD, Massachusetts General Hospital Cancer Center, Boston; Suzanne Louise Topalian, MD, Johns Hopkins University School of Medicine, Baltimore, MD; Jon Wigginton, MD, Dan McDonald, Georgia Kollia, PhD, and Ashok Kumar Gupta, PhD, Bristol-Myers Squibb, Princeton, NJ; and Jeffrey Alan Sosman, MD, Vanderbilt University Medical Center, Nashville, TN.

The study was funded by Bristol-Myers-Squibb.

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