Tmunity Therapeutics has halted development of the CAR T therapy in light of patient deaths.
Tmunity’s dual PSMA-specific, TGFβ-resistant CAR modified autologous T-cell therapy was in two clinical trials against solid tumors, but immune effector cell-associated neurotoxicity syndrome (ICANS) has led to two patient deaths.
The study will now be wound down, and work will begin on a new candidate intended to have a better safety profile, with Tmunity aiming to file an IND later this year.
ICANS is known to be a side effect of CAR T therapy, but understanding of the mechanism behind it is still lacking. Tmunity believe it could be related to the use of CAR T therapy in solid tumors, and could pose a challenge to other developers working in the space.
“I think the bottom line is we’re finding that toxicity is different in liquid tumors like leukemia and myeloma from solid tumors like pancreatic cancer or prostate cancer," Carl June, co-founder of Tmunity, commented in an interview. "I think it’s what is called macrophage activation syndrome, which is related to cytokine storms or [cytokine release syndrome], it’s probably caused by different cytokines."