Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8434479 | Cancer Letters | 2018 | 64 Pages |
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.
Keywords
AAVMSLNColony stimulating factor 1 receptorCSF1RIL-12TLR-3PARPLPSIFN-γEpigallocatechin-3-gallateBMMCTGFLUCTAAFITCEGCGTMEtumor-associated antigenAnti-tumor effectimmunotherapyinterferon-gammainterleukin-12Dendritic cellConnective tissue growth factorphycoerythrinfluorescein isothiocyanateluciferaselipopolysaccharideMesothelinTumor microenvironmentAdeno-associated viruspoly(I:C)poly ADP ribose polymerasePolyinosinic:polycytidylic acidToll-like receptor 3
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Authors
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng,