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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 apoptosi...

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Detalles Bibliográficos
Autores principales: Zhou, Zhanwei, Yang, Ruoxi, Dong, Jingwen, Di, Yongxiang, Yang, Ying, Huang, Ying, Yang, Xue, Liu, Wei, Wang, Jinqiang, Liu, Peifeng, Gu, Zhen, Sun, Minjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674288/
https://www.ncbi.nlm.nih.gov/pubmed/36399575
http://dx.doi.org/10.1126/sciadv.abq4659
Descripción
Sumario: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.