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  3. A personalized vaccine combining immunogenic cell death-induced cells and nanosized antigens for enhanced antitumor immunity

A personalized vaccine combining immunogenic cell death-induced cells and nanosized antigens for enhanced antitumor immunity

  • J Control Release. 2024 Dec:376:1271-1287. doi: 10.1016/j.jconrel.2024.10.060.
Ying Yang 1,  Peng Zheng 2,  Biao Duan 3,  Ying Yang 2,  Xiao Zheng 2,  Weiran Li 2,  Qingwen Liu 3,  Yongmao Hu 4,  Yanbing Ma 5
Affiliations

Affiliations

  • 1 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.935 Jiaoling Road, Kunming 650118, China; Cell Biology & Molecular Biology Laboratory of Experimental Teaching Center, Faculty of Basic Medical Science, Kunming Medical University, Chunrong West Road, Kunming 650500, China.
  • 2 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.935 Jiaoling Road, Kunming 650118, China.
  • 3 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.935 Jiaoling Road, Kunming 650118, China; Kunming Medical University Graduate School, Chunrong West Road, Kunming 650500, China.
  • 4 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.935 Jiaoling Road, Kunming 650118, China; School of Life Sciences, Yunnan University, No.2 Cuihu North Road, Kunming 650091, China.
  • 5 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.935 Jiaoling Road, Kunming 650118, China; State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: MolecularImmunology@imbcams.com.cn.
PMID: 39515613 DOI: 10.1016/j.jconrel.2024.10.060
Abstract

The tumor vaccine aims to activate the immune system, promote antitumor cellular responses, and restore immune recognition and clearance of tumor cells. However, the low immunogenicity and heterogeneity of tumor antigens, along with immunosuppressive mechanisms, severely hinder tumor vaccines from achieving an efficient and sustained antitumor effect. Herein, we developed a combined vaccine strategy that utilizes immunogenic cell death (ICD) to elicit a broad spectrum of antigen-specific responses in a whole-cell-based manner. Additionally, we introduced nanosized antigens to intensify immune responses targeting a key tumor antigen. The combination of mitoxantrone (MTX) and curcumin (Cur) optimized ICD properties in TC-1 tumor cells, as evidenced by increased release of "find me" signals, such as HMGB1 and ATP, and enhanced exposure of the "eat me" signal, CALR, compared to either MTX or Cur alone. Correspondingly, the ICD cells induced by the combination produced more significant antitumor effects in vivo. Furthermore, the ICD cells in combination with E7-HBcAg VLPs or E7-Q11 nanofibers induced more intense effector cell responses to the antigen included in the nanovaccines, as well as a broad spectrum of antigens provided by tumor cells, and significantly suppressed the growth of established tumors compared with either ICD cells, VLPs, or nanofibers alone. In conclusion, the combination of ICD cells and nanosized antigens produced synergistic antitumor effects and elicited robust and comprehensive antitumor immunity, presenting an attractive strategy for developing personalized tumor vaccines.

Keywords

Antitumor immunity; Immunogenic cell death; Nanovaccine; Personalized tumor vaccine; Tumor antigen.

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