The efficacy of chimeric antigen receptor (CAR)-T cell therapy in treating solid tumors remains limited, mainly due to insufficient tumor infiltration and the immunosuppressive tumor microenvironment. This paper proposes a simple and effective strategy for generating activated CAR-T mimetic cells and enabling them to migrate to tumor tissues through magnetic guidance, thereby achieving more potent and precise treatment of solid tumors. By functionalizing magnetic nanoparticles with anti-CD3 antibody (aCD3) and anti-PDL1 antibody (aPDL1), we developed magnetic bispecific nanobody (M-BiNanoAb), which effectively acts on circulating T cells after intravenous injection and reprograms them into CAR-T-like effector cells. In this design, the aPDL1 and aCD3 segments respectively simulate the antigen recognition domain and signal transduction domain of the traditional CAR structure. Surprisingly, by strategically utilizing an external magnetic field, these bioengineered T cells can precisely move to the tumor tissue regions, thereby promoting the elimination of PDL1-overexpressing cancer cells. In preclinical models of solid tumors, this magnetic guidance strategy for generating and controlling CAR-T mimetic cells demonstrates outstanding anti-tumor activity, highlighting its transformative potential in advancing CAR-T-based treatments for solid malignant tumors. This research was published in Advanced Materials under the title "In Vivo Generation and Manipulation of CAR-T-like Cells via Magnetic Bispecific Nano-antibody for Solid Tumor Therapy".
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DOI: 10.1002/adma.202520493