Preclinical development and selection of nanobody-based CAR-T cells targeting HER2-positive solid tumors.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy revolutionized treatment of hematological malignancies, but translation to solid tumors remains difficult. Therefore, different avenues are explored to develop novel CAR-T cell products. Nanobodies have advantageous features for CAR design, such as ease of engineering and low immunogenicity, but predictive values on nanobody characteristics for optimal CAR-T cell function remain unclear. We performed a side-by-side evaluation of 12 nanobody-based (nano)CARs against human epidermal growth factor receptor 2 (HER2). All nanoCARs showed the ability to activate a reporter T cell line upon recognition of HER2^pos cells. When evaluated in primary T cells, 6/12 nanoCARs showed the strongest reactivity and cytotoxicity against HER2^pos

SUBMITTER: Meeus F 

PROVIDER: S-EPMC12686690 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature