4.7 Article

The Adjuvant of a-Galactosylceramide Presented by Gold Nanoparticles Enhances Antitumor Immune Responses of MUC1 Antigen-Based Tumor Vaccines

Journal

INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 16, Issue -, Pages 403-420

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S273883

Keywords

MUC1 glycopeptide; alpha-galactosylceramide; gold nanoparticle; antitumor; vaccine

Funding

  1. National Natural Science Foundation of China [22077068]
  2. National Key R&D Program of China [2018YFA0507204]
  3. NCC Fund [NCC2020FH12]
  4. Natural Science Foundation of Tianjin [19JCQNJC05300]
  5. Fundamental Research Funds for the Central Universities

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This study aimed to enhance the immune effect of MUC1 glycopeptide antigen-based antitumor vaccines by developing novel adjuvants and carriers. The constructed vaccines showed significant antibody response, specific binding with MUC1 positive cells, and induction of MUC1-specific CTLs. Overall, the use of alpha-GalCer adjuvant and antigen on gold nanoparticles offers a potential strategy to improve antitumor response in cancer immunotherapy.
Background: Therapeutic tumor vaccines are one of the most promising strategies and have attracted great attention in cancer treatment. However, most of them have shown unsatisfactory immunogenicity, there are still few available vaccines for clinical use. Therefore, there is an urgent demand to develop novel strategies to improve the immune efficacy of antitumor vaccines. Purpose: This study aimed to develop novel adjuvants and carriers to enhance the immune effect of MUC1 glycopeptide antigen-based antitumor vaccines. Methods: An antitumor vaccine was developed, in which MUC1 glycopeptide was used as tumor-associated antigen, alpha-GalCer served as an immune adjuvant and AuNPs was a multivalent carrier. Results: Immunological evaluation results indicated that the constructed vaccines enabled a significant antibody response. FACS analysis and immunofluorescence assay showed that the induced antisera exhibited a specific binding with MUC1 positive MCF-7 cells. Moreover, the induced antibody can mediate CDC to kill MCF-7 cells. Besides stimulating B cells to produce MUC1-specific antibodies, the prepared vaccines also induced MUC1-specific CTLs in vitro. Furthermore, the vaccines significantly delayed tumor development in tumor-bearing mice model. Conclusion: These results showed that the construction of vaccines by presenting alpha-GalCer adjuvant and an antigen on gold nanoparticles offers a potential strategy to improve the antitumor response in cancer immunotherapy.

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