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    Anticancer Vaccination with Immunogenic Micelles That Capture and Release Pristine CD8(+) T-Cell Epitopes and Adjuvants

    Year: 2022

    Journal: ACS Appl. Mater. Interfaces, Volume 14, JAN 19, page 2510–2521

    Authors: Ren, He; Li, Jiexin; Liu, Gengqi; Sun, Yaping; Yang, Xingyue; Jiang, Zhen; Zhang, Jingyu; Lovell, Jonathan F.; Zhang, Yumiao

    Organizations: National Key Research and Development Program [2021YFC2102300]; National Natural Science Foundation of China [32071384]; Startup Grant at Tianjin University; One-thousand Young Talent Program of China

    Keywords: self-immolation; hydrophobic modification; traceless release; immunogenic micelles; cancer immunotherapy

    The development of nanocarriers capable of codelivering antigens and immune-activating adjuvants is an emerging area of research and is relevant for cancer vaccines that target induction of antigen-specific CD8(+) T-cell responses. Here, we report a system for delivery of short peptide antigens to dendritic cells for strong cellular immune responses, based on block copolymers chemically modified with a hydrophobic and self-immolative linker. After modification, micelles effectively and reversibly capture antigens and adjuvants via a covalent bond within several minutes in an aqueous solution. After uptake in antigen presenting cells, the polymer disulfide bond is cleaved by intracellular glutathione, leading to release of pristine antigens, along with the upregulated expression of costimulatory molecules. The induced antigen-specific CD8(+) T cells have strong tumor cell killing efficacy in the murine B16OVA and human papilloma virus-E6/E7 subcutaneous and lung metastasis tumor models. In addition, delivery to lymph nodes can be imaged to visualize vaccine trafficking. Taken together, multifunctional self-immolative micelles represent a versatile class of a vaccine delivery system for the generation of a cellular immune response that warrants further exploration as a component of cancer immunotherapy.
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