B7-H3 nanobody-based CAR T cells control multiple myeloma growth, while dual BCMA/B7-H3 CAR T cells overcome antigen escape.

ABSTRACT:

Background

CAR T cell therapy targeting BCMA has shown remarkable efficacy in multiple myeloma (MM), but relapses occur due to T cell exhaustion and the emergence of BCMA-negative subpopulations. Novel targets are needed to overcome antigen escape.

Methods

B7-H3 (CD276) expression was assessed on primary MM patient samples. We engineered nanobody-based CAR T cells (nanoCARs) targeting B7-H3 and evaluated their cytotoxicity and cytokine production in vitro, including against patient-derived myeloma cells. Anti-tumor activity was tested in two different MM xenograft models. Dual CAR T cells (BCMA/B7-H3) and CARpooling (mix of BCMA and B7-H3 CAR T cells) were also tested for efficacy in antigen escape models.

Results

B7-H3 expression was detected on plasma cells in 60% o

SUBMITTER: Van der Vreken A 

PROVIDER: S-EPMC12619266 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature