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 has approved two anti-PD-1 antibodies, nivolumab and pembrolizumab, for patients with advanced melanoma 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 are known to “wake up” immune cells that can attack cancer and have been hailed as one of the first cancer immunotherapy success stories. But Tobias Schatton, PhD, of BWH’s Department of Dermatology and his colleagues at BWH, Boston Children’s Hospital and elsewhere wondered if this might not be the whole story: in addition to interacting with cells in the immune system, could the antibodies be interacting with other kinds of cells to fight cancer?

Melanoma cells. Image courtesy of the NCI Center for Cancer Research.

To find out, the research team explored human and mouse melanoma cell lines as well as patient melanoma samples. They 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.

“Cancer immunotherapies – therapies that activate the immune system to target cancer – have worked in melanoma in the past, but never this well. 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,” said corresponding author Schatton.

The new study represents a highly collaborative effort among researchers including Sonja Kleffel, Christian Posch, Steven Barthel, Hansgeorg Mueller, Christoph Schlapbasch, Emmanuella Guenova, Christopher Elco, Nayoung Lee, Viram Juneja, Qian Zhan, Christine Lian, Rahel Thomi, wolfram Hoetzenecker, Antonio Cozzio, Reinhard Drummer, Martin C. Mihm, Jr., Keith T. Flaherty, Markus H. Frank, George Murphy, Arlene Sharpe, and Thomas Kupper.