Preclinical evaluation of antigen-sensitive B7-H3-targeting nanobody-based CAR-T cells in glioblastoma cautions for on-target, off-tumor toxicity

Abstract

B7-H3 nanoCAR-T cells showed promise for glioblastoma therapy following in vitro characterization, but limiting in vivo toxicity was observed. Off-tumor recognition of healthy mouse tissue by the cross-reactive B7-H3 nanoCAR-T cells was identified as a potential cause for this toxicity, warranting caution when using highly sensitive nanoCAR-T cells, recognizing the low-level expression of B7-H3 on healthy tissue.