期刊
HUMAN VACCINES & IMMUNOTHERAPEUTICS
卷 10, 期 11, 页码 3153-3164出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/21645515.2014.980686
关键词
cellular immune response; DNA vaccines; humoral immune response; immune tolerance; tumor antigens; vaccine delivery; TAAs; tumor-associated antigens; CT antigens; cancer-testis antigens; CEA; carcinoembryonic antigen; Id; idiotype; TLRs; Toll-like receptors; IRF; interferon regulatory factor; IFNs; interferons; TBK1; Tank-binding kinase 1; STING; stimulator of interferon genes; APCs; antigen presenting cells; MHC; major histocompatibility complex; CTLs; cytotoxic lymphocytes; EP; electroporation; SCT; single-chain trimer; Trp2; tyrosinase related protein 2; hTERT; human telomerase reverse transcriptase; phTERT; optimized full-length hTERT; NHP; non-human primate; TT; tetanus toxin; DOM; fragment c domain; GITR; glucocorticoid-induced tumor necrosis factor receptor family-related genes; PMED; particle mediated epidermal delivery; HER2; Her2; neu; Mam-A; Mammaglobin-A; PAP; Prostatic acid phosphatase; PSMA; prostate-specific membrane antigen; CIN; cervical intraepithelial neoplasia; HSP70; heat shock protein 70
资金
- National Institutes of Health/National Cancer Institute Cervical Cancer SPORE [P50CA098252]
- Head and Neck Cancer SPORE [P50 CA-DE019032, R43CA174436, 2R01CA114425-06, R01CA142691]
DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety. Results from numerous clinical trials have demonstrated that DNA vaccines are well tolerated by patients and do not trigger major adverse effects. DNA vaccines are also very cost effective and can be administered repeatedly for long-term protection. Despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific cellular immune responses as a result of immune tolerance against endogenous self-antigens in tumors. Strategies to enhance immunogenicity of DNA vaccines against self-antigens have been investigated including encoding of xenogeneic versions of antigens, fusion of antigens to molecules that activate T cells or trigger associative recognition, priming with DNA vectors followed by boosting with viral vector, and utilization of immunomodulatory molecules. This review will focus on discussing strategies that circumvent immune tolerance and provide updates on findings from recent clinical trials.
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