Study tests GD2IL18CART against GD2-positive solid cancers
Fischer-Riepe L, Kailayangiri S, Zimmerman K, et al. Preclinical Development of CAR T Cells With Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers. Clinical Cancer Research. 2024; (doi: 10.1158/1078-0432.CCR-23-3157).
The shortcomings of chimeric antigen receptor (CAR) T cells against solid cancers might be resolved through cytokine engineering, as demonstrated by GD2IL18CART. Still in the preclinical phase, the investigational product is constructed from CAR T cells that target ganglioside GD2 and that, upon engagement with GD2 antigens, manufacture interleukin-18 (IL-18). The result is a more significant activation response, as engineering of human T cells with GD2-specific CAR generate similar numbers of CAR-expressing central memory T cells. Additionally, in response to interaction with GD2-positive tumor cells, GD2IL18CART mediates greater cytokine release and achieves more effective target cytolysis than CAR T cells lacking inducible IL-18. It also appears to exhibit superior antitumor activity in vivo, with GD2-positive tumor xenografts eliminated. These findings provide the foundation for future clinical investigation of GD2IL18CART in children and adults with neuroblastoma and other GD2-positive malignancies.