4.8 Article

Personalized Nanovaccine Coated with Calcinetin-Expressed Cancer Cell Membrane Antigen for Cancer Immunotherapy

Journal

NANO LETTERS
Volume 21, Issue 19, Pages 8418-8425

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c03004

Keywords

Tumor cell membrane; immunogenic cell death; nanoparticles; nanovaccine; immunotherapy

Funding

  1. National Natural Science Foundation of China [51725303, 81701831, 52033007, 52073236]
  2. 5th Chinese Association for Science and Technology Young Talents Support Project

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A novel nanovaccine containing a cell membrane antigen induced by immunogenic cell death was reported, providing a complete antigen array and avoiding severe chemotherapy toxicity. The nanovaccine codelivers adjuvant R837 and membrane antigen, triggering personalized immune responses, enhancing antitumor effects, and providing long-term protection. The surface-exposed calcinetin on the nanovaccine actively uptakes dendritic cells, enhancing antitumor effects, and activating immune memory cells.
A cancer vaccine has been widely applied in clinical tumor therapy as one of the main strategies of immunotherapy. However, the traditional cancer vaccine for a single antigen has a low benefit rate due to the individual differences in patients. Here, we report a R837-loaded poly(lactic-co-glycolic acid) nanovaccine coated with a calcinetin (CRT)-expressed cancer cell membrane antigen for immunotherapy. The cell membrane antigen that possessed a complete antigen array was obtained by inducing immunogenic cell death in vitro, avoiding the severe systemic toxicity of chemotherapy in vivo. The nanovaccine codelivers the adjuvant R837 and the Luc-4T1 membrane antigen, triggering a personalized immune response to the corresponding tumor. Moreover, the calcinetin exposed on the surface of the nanovaccine induces the active uptake of dendritic cells, consequently enhancing the antitumor effect. Meanwhile, the nanovaccine activates immune memory cells to provide long-term protection. Our work provides a new strategy for a clinical personalized antitumor vaccine.

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