Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses. Issue 11 (12th March 2021)

• Record Type: Journal Article
• Authors: Lin, Danmin; He, Huafeng; Sun, Jiajie; He, Xianying; Long, Wei; Cui, Xiping; Sun, Yunxiao; Zhao, Suqing; Zheng, Xi; Zeng, Zheng; Zhang, Kun; Wang, Huaqian
• Is Part Of: Vaccine. Volume 39:Issue 11(2021)
• Page Start: 1609
• Page End: 1620
• Publication Date: 2021-03-12
• Subjects: Subunit vaccine -- mGM-CSF -- PSMA -- Nasal administration -- CTL responses -- DC; APC antigen-presenting cell -- CT cholera toxin -- CTA2 A2 subunit of cholera toxin -- CTB b subunit of cholera toxin -- CTL cytotoxic T lymphocyte -- DC dendritic cell -- EGFP enhanced green fluorescent protein -- mGM-CSF murine granulocyte-macrophage colony stimulating factor -- MTT methylthiazolyldiphenyl-tetrazolium -- IFN-γ interferon-γ -- PSMA prostate specific membrane antigen -- TAA Tumor-associated antigen -- TLR4 Toll-like receptor 4; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.02.002
• Languages: English
• ISSNs: 0264-410X

Abstract

Graphical abstract: Highlights: CT-like chimeric protein enables co-delivery of epitopes and cytokine adjuvant. Nasal administration of CT-like chimeric protein delayed the prostate tumor growth. CT-like chimeric protein boosts CTL effects by promoting the maturation of DC. Platform for screening PSMA specific epitopes in prostate cancer immunotherapy. Abstract: Subunit vaccines derived from tumor antigens play a role in tumor therapy because of their unique advantages. However, because of the weak immunogenicity of peptides in subunit vaccines, it is difficult to trigger an effective cytotoxic T lymphocyte (CTL) response, which is critical for cancer therapy. A requirement for the activation of CTL cells by exogenous antigens is the stimulation of antigen presenting cells (APC) with the help of adjuvants and cross-presentation to T lymphocytes. Standard nonconjugated adjuvant-peptide mixtures do not ensure co-targeting of the antigen and the adjuvant to the same APC, which limits the effects of adjuvants. In this study, a fusion protein consisting of murine granulocyte-macrophage colony stimulating factor (mGM-CSF) fused with CTA2 (A2 subunit of cholera toxin) was generated and assembled with CTB-PSMA624-632 (prostate specific membrane antigen (PSMA) peptide 624–632 fused to CTB) to obtain a cholera toxin-like protein. The chimeric protein retained the biological activity of mGM-CSF and had stronger GM1 binding activity than (CTB-PSMA624-632)5. C57BL/6J mice immunized with the CT-like chimeric protein exhibited delayed tumor growth following challenge with human PSMA-EGFP-expressing RM-1 cells. Experiment results showed that the CT-like chimeric protein could induce the maturation of DC cells and improve CTL responses. Overall, these results indicate that the nasal administration of a CT-like chimeric protein vaccine results in the development of effective immunity against prostate tumor cells and might be useful for future clinical anti-tumoral applications.