Targeting oncofetal tenascin C with immunotherapy requires a signal boost

Chimeric antigen receptor (CAR) T–cell therapy, an immunotherapy that reprograms a patient’s immune cells to target cancer proteins, has shown some success in pediatric blood cancers but not solid or brain tumors. St. Jude scientists previously used a computational approach to discover new potential CAR T–cell targets in solid and brain tumors, finding variants of the extracellular protein oncofetal tenascin C (TNC) as a candidate. In a new study spearheaded by PhD student Elizabeth Wickman, St. Jude Graduate School of Biomedical Sciences, in the lab of Stephen Gottschalk, MD, St. Jude Department of Bone Marrow Transplantation & Cellular Therapy chair, oncofetal TNC could be effectively targeted if T cells expressed not only TNC-specific CARs but also chimeric cytokine receptors (CCRs) that activate interleukin-18 signaling pathways. Findings were published recently in the Journal for Immunotherapy of Cancer.

“Our study highlights that it is feasible to exploit oncofetal splice variants of extracellular matrix proteins such as TNC as targets for CAR T–cell therapy for pediatric cancers,” said Gottschalk. “Likewise, it highlights the benefit of expressing CCRs in CAR T cells to boost their activity.”

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