Immuno-modulators enhance antigen-specific immunity and anti-tumor effects of mesothelin-specific chimeric DNA vaccine through promoting DC maturation. (1st July 2018)

• Record Type: Journal Article
• Authors: Chen, Yu-Li; Chang, Ming-Cheng; Chiang, Ying-Cheng; Lin, Han-Wei; Sun, Nai-Yun; Chen, Chi-An; Sun, Wei-Zen; Cheng, Wen-Fang
• Is Part Of: Cancer letters. Volume 425(2018)
• Page Start: 152
• Page End: 163
• Publication Date: 2018-07-01
• Subjects: Mesothelin -- Dendritic cell -- Anti-tumor effect -- Mesothelin-expressing tumor -- Immunotherapy; MSLN mesothelin -- CTGF connective tissue growth factor -- TAA tumor-associated antigen -- CSF1R colony stimulating factor 1 receptor -- TME tumor microenvironment -- EGCG epigallocatechin-3-gallate -- AAV adeno-associated virus -- IL-12 interleukin-12 -- IFN-γ interferon-gamma -- PE phycoerythrin -- FITC fluorescein isothiocyanate -- Luc luciferase -- poly(I:C) polyinosinic:polycytidylic acid -- PARP poly ADP ribose polymerase -- BMM bone marrow monocyte -- LPS lipopolysaccharide -- DC dendritic cell -- TLR-3 toll-like receptor 3; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.03.032
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand–poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes. An increase in MSLN-specific CD8 + T cells and anti-MSLN Ab titers was also noted in CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice. The CTGF/MSLN DNA vaccine combined with immuno-modulator EGCG also generated potent anti-tumor effects. Immuno-modulators could enhance the antigen-specific anti-tumor effects of CTGF/MSLN DNA vaccine through promoting the DC maturation. In addition, MSLN-specific cell-based vaccine with AAV-IL-12 and the CTGF/MSLN DNA vaccine with anti-CD40Ab/polyp(I:C) generated more potent anti-tumor effects than the other combinational regimens. The results indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be an effective immunotherapeutic strategy to control MSLN-expressing tumors including ovarian and pancreastic cancers, and malignant mesothelioma. Highlights: Mesothelin (MSLN) can be identified and immunogenic in various malignancies. MSLN-specific DNA vaccine combined with immuno-modulators can be an effective strategy to control MSLN-expressing tumors. Immuno-modulators could enhance the anti-tumor effects of CTGF/MSLN DNA vaccine through promoting the maturation of DCs.