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Pore forming-mediated intracellular protein delivery for enhanced cancer immunotherapy.

ABSTRACT: 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.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC9674288 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Pore forming-mediated intracellular protein delivery for enhanced cancer immunotherapy.

Zhou Zhanwei Z Yang Ruoxi R Dong Jingwen J Di Yongxiang Y Yang Ying Y Huang Ying Y Yang Xue X Liu Wei W Wang Jinqiang J Liu Peifeng P Gu Zhen Z Sun Minjie M

Science advances 20221118 46

Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8<sup>+</sup> 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<sup>+</sup> T cell-mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and ...[more]

PMID: 36399575

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