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

Abstract

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, α-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 α-GalCer adjuvant and an antigen on gold nanoparticles offers a potential strategy to improve the antitumor response in cancer immunotherapy.

MUC1: Structure, Function, and Clinic Application in Epithelial Cancers

“…NPs have been developed to deliver mRNA vaccines that encode the tumor antigen MUC1 to DCs in lymph nodes, thereby facilitating the activation and expansion of tumor-specific T cells [ 103 ]. The construction of MUC1 glycopeptide vaccines by presenting α-GalCer adjuvants and antigens on gold NPs has also been proposed; this technique can potentially enhance anti-tumor responses during cancer immunotherapy [ 104 ]. The MUC1 vaccine has been tested in combination with other drugs to increase its anti-tumor effects.…”

Targeting Sphingolipids for Cancer Therapy

“…Preclinical and clinical trials using α-GalCer have shown that this therapy is safe, exhibits durable activation, and increases the number of iNKT, NK, tumor-specific, CD4+, CD8+ T, and B cells ( 148 , 149 , 151 , 153 – 156 , 160 , 161 , 169 , 172 , 173 , 175 ). This activation is associated with increased serum levels of cytokines that stimulate the growth and function of T cells [IL-12 ( 150 , 175 ) and IL-2 receptors ( 175 )] and other factors that enhance natural killer cell activity (i.e., interferon gamma [IFN-γ] ( 150 , 155 , 156 , 158 , 161 , 163 , 172 ), CD16 ( 175 ), and tumor necrosis factor α [TNF-α]) and immune cell maturation (GMCSF) ( 164 ).…”

Multifunctional inorganic nanomaterials for cancer photoimmunotherapy

“…Furthermore, this treatment modality could potentially be applied in cancer metastasis treatment because a systemic anti-tumor immune reaction could be induced through the therapeutic agent DOX and PTT [109]. The capability of AuNPs to load and release nucleic acids exhibits great research potential in cancer immunotherapy, because PTT-induced hyperthermia or light-triggered drug release can be synergistically achieved with the delivery of nucleic acid immunoadjuvants, which protects these bio-therapeutics from inactivation or degradation [110]. For instance, it was reported that AuNPs can improve the effectiveness of CpG both in vitro and in vivo [111][112][113].…”