5 Things to Know About the Next Wave of Cancer Immunotherapy

Immunotherapy changed the game

Instead of poisoning every fast-dividing cell the way chemotherapy does, immunotherapy recruits the body’s own immune system to find and destroy cancer — usually with far fewer side effects.

But it has a reach problem

The blockbuster checkpoint inhibitors — Keytruda, Opdivo and others — only work against tumors that hide using the PD-L1 pathway. That’s roughly 20% of solid tumors. The other 80% are left out.

Tumors have more than one hiding place

One of the biggest alternatives is an enzyme called ENPP1. When tumors over-express it, ENPP1 destroys cGAMP — the ‘something’s wrong’ alarm cells send to the immune system — so the cancer grows undetected. About half of solid tumors use this trick.

A new class of drugs is going after it

ENPP1 inhibitors aim to switch that alarm back on. Cyana Therapeutics is developing one such candidate, CY-3132, tested across tumor types that have long resisted treatment:

“By blocking ENPP1 activity, CY-3132 transforms tumor cells from immune evading to immune activating.”— Dr. Shoshana Shendelman, CEO, Cyana Therapeutics

The prize is enormous

If these next-generation targets pan out, immunotherapy’s benefits could extend to the large majority of patients it currently can’t help — the real goal driving the field forward.