Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies

Chimeric-antigen-receptor (CAR) T-cell therapy for CD19-expressing B-cell malignancies is already widely adopted in clinical practice. On the other hand, development of CAR-T-cell its nascent stage. One potential targets CD26, to which we have developed and evaluated efficacy safety humanized monoclonal antibody YS110. We generated second (CD28) third (CD28/4-1BB) generation CD26-targeted CAR-T-cells (CD26-2G/3G) using YS110 as single-chain variable fragment. When co-cultured with CD26-overexpressing target cells, CD26-2G/3G strongly expressed activation marker CD69 secreted IFNgamma. In vitro studies targeting leukemia cell line HSB2 showed that exhibited significant anti-leukemia effects secretion granzymeB, TNFα, IL-8, 3G being superior 2G. was also highly effective against lymphoma cells derived from patients. an vivo mouse model a line, KARPAS299, transplanted subcutaneously, CD26-3G inhibited tumor growth, whereas 2G had no effect. Furthermore, systemic dissemination administered intravenously, growth more potently than 2G, resulting greater survival benefit. The third-generation may be promising treatment modality malignancies.