Armored CAR-Ts? Memorial Sloan Kettering engineers CAR-T loaded with checkpoint inhibitors

Scientists at Memorial Sloan Kettering have engineered a hybrid cancer therapy that might just bring two of hottest areas of oncology science together in one package: CAR-T and checkpoint inhibitors.

Sarwish Rafiq

That’s the hope of a team of MSK researchers working in the labs of Renier Brentjens, a renowned physician-scientist in New York City. They just published a paper in Nature — authored by Sarwish Rafiq, Oladapo Yeku, and Hollie Jacksonoutlining their success in animal models.

“We took a step back and said, ‘How can we make CAR T cells better?’ That’s when we decided to try to combine these two promising approaches,” Brentjens said. “This proves — at least in a mouse model — that we can now have our cake and eat it too.”

Oladapo Yeku

The early research is promising. Here’s how it works: MSK’s newly designed CAR-T cells come loaded with a miniature version of a checkpoint-blocking antibody, similar to drugs already on the market like Opdivo and Keytruda. When the loaded CAR-T is delivered to the tumor environment, the antibodies are secreted — binding to PD-1 proteins and slamming the brakes on immune cells. This allows the CAR-Ts to better fight the cancer cells, with an army of antibodies by their side.

MSK is calling this new tech an “armored CAR T.” They made two versions of it: one that recognizes CD19 (found in certain blood cancers), and the other that recognizes MUC16, which is found in some ovarian and pancreatic cancers.

In mouse models, the researchers found that mice on the armored CAR treatment lived significantly longer than those on regular CARs, and the armored CARs stuck around in the body longer, too. Plus, the checkpoint drugs released by the CAR-Ts created a helpful bystander effect, and PD-1 antibodies were low in circulating blood (hopefully indicating that the treatment wasn’t spreading beyond the tumor site).

“An armored CAR T approach represents the next phase of innovation in T cell therapies,” Brentjens said in a news release. “These data, together with in vivo models, suggest that this is an early step toward exploring how we can make the first iterations of CAR T cell therapies even better.”

MSK says it’s in the process of designing clinical trials in humans.

Photo: Renier J. Brentjens. Memorial Sloan Kettering

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