This study developed a magnetic bispecific nanobody (M-BiNanoAb) that can bind to circulating T cells in vivo via intravenous administration, transforming them in situ into CAR-T-like cells with targeting and killing functions. The nanobody surface is modified with both anti-CD3 and anti-PD-L1 antibodies, which mimic the signaling domain and antigen recognition domain of CAR structures, respectively, enabling T cells to specifically recognize and eliminate tumor cells with high PD-L1 expression.Crucially, with the guidance of an external magnetic field, these engineered cells can migrate directionally and effectively infiltrate solid tumors, significantly enhancing T cell accumulation and activation within the tumor microenvironment. In various preclinical models, such as melanoma and breast cancer, this strategy has demonstrated over 90% tumor suppression and can stimulate antigen epitope spreading and long-lasting immune memory, providing a new approach to immunotherapy for solid tumors that combines targeting, controllability, and potency.

Reference News:

DOI: 10.1002/adma.202520493