Why does a new class of drugs work so well against melanoma?

nivolumab, pembrolizumab and melanoma
Anti-PD-1 antibodies may deliver a one-two punch in melanoma

Recent clinical trials for patients with advanced melanoma have found that a new class of drugs—anti-PD-1 antibodies—can elicit an unprecedented response rate. In the last year, the FDA gave accelerated approval to two anti-PD-1 antibodies, nivolumab and pembrolizumab, for patients with advanced melanoma (including Jimmy Carter) who are no longer responding to other drugs. And there’s growing evidence that this class of drugs may be effective in treating other forms of cancer.

Anti-PD-1 antibodies target a receptor on activated T cells, known as the programmed cell death 1 (PD-1) receptor. Tumor cells stimulate this inhibitory receptor to dodge immune attack, whereas anti-PD-1 antibodies block the same pathway, “waking up” the immune cells so they can attack the cancer. The drugs have been hailed as one of the first cancer immunotherapy success stories.

melanoma immunotherapyBut Tobias Schatton, PhD, PharmD, of Brigham and Women’s Hospital (BWH), along with colleagues at BWH, Boston Children’s Hospital and elsewhere, wondered if this was the whole story.

Looking at human and mouse melanoma cell lines, as well as patient melanoma samples, the research team found that not only the immune cells, but also the cancer cells themselves expressed the targets of anti-PD-1 antibodies. In addition to awakening an immune attack on cancer cells, the antibodies also appeared to inhibit tumor growth by targeting cancer cells directly. Their results appear in the September 10 issue of Cell.

Anti-PD-1 antibodies inhibit melanoma

“Cancer immunotherapies—therapies that activate the immune system to target cancer—have worked in melanoma in the past, but never this well,” says Schatton, the study’s senior investigator. “Now we have found a possible new explanation for why: this is a class of drugs that may target both the immune system and the tumor itself.”

Haley Bridger is a science writer at Brigham and Women’s Hospital.