Pore forming-mediated intracellular protein delivery for enhanced cancer immunotherapy

Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8+ T cells to form pores on the tumor cells' plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8+ T cell-mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer. Notably, three courses of laser irradiation induced efficient cell apoptosis and immune activation, resulting in a notable therapeutic efficacy that 75% of the tumors were ablated without relapse.

Automated summary

In this study, the researchers successfully utilized CD8+ T cells to form pores on tumor cells' plasma membranes, enabling the delivery of RNase A and granzyme B into cells. This effectively induced tumor apoptosis and pyroptosis through the activation of caspase 3 and gasdermin E pathways, enhancing the efficacy of CD8+ T cell-mediated immunotherapy.