DNTGF-βR armored CAR-T cell therapy against tumors from bench to bedside

Abstract

TGF-β, a negative cytokine, exerts critical roles in shaping immunosuppressive TME, thereby promoting tumor progression and resistance [1]. [...]evolving approaches to blocking TGF-β signaling in CAR-T cell therapy have been emerging, such as combining with TGF-β-targeted neutralizing antibodies or small molecule inhibitors, directly deleting TGF-βRII via CRISPR/Cas9 technology, or co-expressing a dominant-negative TGF-β receptor II (DNTGF-βRII). Table S2). [...]solid tumors were ideal indications for DNTGF-βR armored CAR-T cell therapy due to the crucial negative role of TGF-β in TME (Fig. 1D). Additionally, a recent study reported that a CD200R-CD28 switch optimally outperformed in enhancing CAR-T function in CD200 + multiple myeloma (MM) models than the approach of CD200R-dominant negative [6].