AbClon patents switchable CAR-T using nicotine byproduct as FDA eases oversight

For a decade, CAR-T therapies such as Bristol Myers Squibb’s Abecma and Breyanzi, Gilead Sciences’ Yescarta and Tecartus, Johnson & Johnson and Legend’s Carvykti, and Novartis’ Kymriah have delivered eye-popping remission rates in blood cancers like leukemia, lymphoma, and myeloma.

These cancers circulate through the bloodstream, giving CAR-T cells a direct path to their target. Solid tumors are different. They bury themselves in hostile microenvironments that block and suppress immune cells before they can act.

AbClon, a Korean biotech, believes it has a workaround. The company’s U.S. patent, published in June, outlines a two-part system that gives doctors external control over when and where the cells go to work.

“We inject the switch molecule first,” AbClon CEO Lee Jong-seo said in a phone call with Korea Biomedical Review on Wednesday. “The affibody finds the tumor, the cotinine acts as a bridge to call in the CAR-T cells. In short, the affibody tags the cancer, cotinine hooks the CAR-T, and that’s how we drive the therapy exactly where it needs to go.”

The first piece of the system is the zCAR-T cell, engineered to recognize cotinine, a nicotine byproduct that does not occur naturally in the body. The second is a switch molecule that links cotinine to an anti-HER2 affibody, which Lee said is about one-twenty-fifth the size of a standard antibody. 

Once the affibody binds to tumor tissue, the cotinine serves as a tether, activating the zCAR-T cells only at the intended site.

That switch is the core of AbClon’s pitch. Without cotinine, Lee says the T cells stay dormant. Once the molecule is cleared -- “typically within 24 hours” -- the therapy shuts off. “If we infused these cells without any cotinine in the system, nothing would happen,” Lee said.

That kind of on-off control could sidestep one of the biggest safety concerns in CAR-T. Traditional therapies can linger in the body for weeks, risking prolonged immune activation, cytokine storms, neurotoxicity, and off-target damage. 

By contrast, AbClon says its switchable system allows for a tighter therapeutic window and tunable dosing.

Asked why the company picked cotinine, Lee said the company needed a trigger molecule that doesn't exist in the body and is proven to be safe at relatively high doses. “If we made antibodies targeting substances already present, the CAR-Ts could attack normal tissue,” he said.

According to preclinical data cited by the company, cytotoxicity in HER2-positive tumor models increases with the cotinine dose. “It’s basically volume control for T-cell killing,” Lee said.

The patent arrives just as the FDA has loosened guardrails on the entire CAR-T category. On June 26 (U.S. time), the agency dropped its Risk Evaluation and Mitigation Strategy, or REMS, requirements for all approved CD19- and BCMA-targeted CAR-Ts. 

The REMS framework had long been seen as a bottleneck, requiring hospitals to be specially certified and forcing patients to stay near treatment centers for weeks after infusion.

“Regulatory burdens often mean expensive manufacturing and strict QC processes, which is why CAR-T therapies cost so much,” Lee said. “With looser regulations, manufacturers like us can lower production costs. Also, CAR-T has mostly been used as a last-line treatment so far, but this could help move it into earlier lines of therapy, increasing patient access and market size.”