OSE details novel immuno-oncology strategy targeting 'don't eat me' signaling in cancer

OSE details novel immuno-oncology strategy targeting 'don't eat me' signaling in cancer

One of the most sought-after targets in immuno-oncology over the past few years is “don’t eat me” signaling, a process by which tumors escape destruction by preventing immune cells from detecting, engulfing and destroying them. OSE Immunotherapeutics is among the companies pursuing this signaling pathway, and it has unveiled preclinical data supporting a novel strategy for disrupting it.

The company is focusing on C-type lectin receptor (CLEC-1), a recently discovered checkpoint that blocks the ability of the immune system’s myeloid cells to engulf cancer cells, which in turn prevents T cells from waging an attack on tumors. OSE has developed antibodies to block CLEC-1.

In preclinical studies, blocking CLEC-1 ramped up the destruction of cancer cells by myeloid cells, OSE reported during the Society for Immunotherapy of Cancer (SITC) virtual conference. The strategy was even more effective when combined with chemotherapy, the company said.

“When we evaluated mice deficient in CLEC-1, we found that they spontaneously reject several types of tumors, and there is an increased T-cell response,” said Nicolas Poirier, Ph.D., chief scientific officer of OSE, in an interview with Fierce BiotechResearch.

OSE researchers studied CLEC-1 expression in human tumor cells and discovered that the checkpoint becomes especially abundant after chemotherapy, suggesting that it boosts don’t-eat-me signaling in cancer cells that are damaged and close to dying. Inhibiting CLEC-1 in conjunction with chemotherapy produced “efficient and robust anti-tumor immune responses,” the company reported.

The popularity of blocking “don’t eat me” signaling in cancer was borne out in Gilead Sciences' $4.9 billion acquisition of Forty Seven earlier this year. Forty Seven, a Stanford University spinout, developed a drug to block CD47, which is expressed by cancer stem cells to facilitate don’t-eat-me signaling.

Several other companies are working on CD47 inhibitors, including Arch Oncology. It presented data at SITC demonstrating how its anti-CD47 antibody, AO-176, binds to tumor cells while leaving health cells alone. Arch raised $50 million in a series B funding last year from Roche Venture Fund and other investors.

The next step for OSE is to further evaluate its lead anti-CLEC-1 antibodies in the hopes of selecting one for clinical development in the first quarter of next year, Poirier said. Additional preclinical studies will be needed to determine which tumors are most amenable to CLEC-1 inhibition, he added.

OSE is also studying the potential of combining CLEC-1 inhibition with drugs that block the well-known immune checkpoint PD-1. “We will be looking to see if a double-checkpoint approach might increase the durability of the T-cell response,” he said.

Source: https://www.fiercebiotech.com/