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Antigen Capture and Immune Modulation by Bacterial Outer Membrane Vesicles as In Situ Vaccine for Cancer Immunotherapy Post-Photothermal Therapy

Published:12 February 2022 DOI: 10.1002/smll.202107461 PMID: 35152555
Yao Li, Kaiyue Zhang, Yao Wu, Yale Yue, Keman Cheng, Qingqing Feng, Xiaotu Ma, Jie Liang, Nana Ma, Guangna Liu, Guangjun Nie, Lei Ren, Xiao Zhao

Abstract

Tumor antigens released from tumor cells after local photothermal therapy (PTT) can activate the tumor-specific immune responses, which are critical for eliminating the residual lesions and distant metastases. However, the limited recognition efficiency of released tumor antigens by the immune system and the immunosuppressive microenvironment lead to ineffective antitumor immunity. Here, an in situ multifunctional vaccine based on bacterial outer membrane vesicles (OMVs, 1-MT@OMV-Mal) is developed by surface conjunction of maleimide groups (Mal) and interior loading with inhibitor of indoleamine 2, 3-dioxygenase (IDO), 1-methyl-tryptophan (1-MT). 1-MT@OMV-Mal can bind to the released tumor antigens after PTT, and be efficiently recognized and taken up by dendritic cells. Furthermore, in situ injection of 1-MT@OMV-Mal simultaneously overcomes the immune inhibition of IDO on tumor-infiltrating effector T cells, leading to remarkable inhibition on both primary and distant tumors. Together, a promising in situ vaccine based on OMVs to facilitate immune-mediated tumor clearance after PTT through orchestrating antigen capture and immune modulation is presented.

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