DNA vaccine for cancer immunotherapy

• Published in: Human vaccines & immunotherapeutics Vol. 10; no. 11; pp. 3153 - 3164
• Main Authors: Yang, Benjamin, Jeang, Jessica, Yang, Andrew, Wu, T C, Hung, Chien-Fu
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2014
• Subjects: Animals; Antigens, Neoplasm - immunology; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; cellular immune response; Dendritic Cells - immunology; DNA vaccines; Humans; humoral immune response; immune tolerance; Immunotherapy - methods; Mice; Neoplasms - immunology; Neoplasms - prevention & control; Neoplasms - therapy; Reviews; tumor antigens; Tumor Escape - immunology; Vaccination; vaccine delivery; Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use; IRF, interferon regulatory factor; cellular immune response; CTLs, cytotoxic lymphocytes; SCT, single-chain trimer; CEA, carcinoembryonic antigen; HER2, Her2/neu; phTERT, optimized full-length hTERT; CIN, cervical intraepithelial neoplasia; DNA vaccines; PMED, particle mediated epidermal delivery; hTERT, human telomerase reverse transcriptase; tumor antigens; HSP70, heat shock protein 70; TBK1, Tank-binding kinase 1; immune tolerance; STING, stimulator of interferon genes; APCs, antigen presenting cells; Id, idiotype; DOM, fragment c domain; Mam-A, Mammaglobin-A; NHP, non-human primate; EP, electroporation; humoral immune response; MHC, major histocompatibility complex; TAAs, tumor-associated antigens; Trp2, tyrosinase related protein 2; CT antigens, cancer-testis antigens; IFNs, interferons; TLRs, Toll-like receptors; PSMA, prostate-specific membrane antigen; vaccine delivery; PAP, Prostatic acid phosphatase; TT, tetanus toxin; GITR, glucocorticoid-induced tumor necrosis factor receptor family-related genes
• ISSN: 2164-5515; 2164-554X
• DOI: 10.4161/21645515.2014.980686

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.