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.
Keywords: APCs, antigen presenting cells; CEA, carcinoembryonic antigen; CIN, cervical intraepithelial neoplasia; CT antigens, cancer-testis antigens; CTLs, cytotoxic lymphocytes; DNA vaccines; DOM, fragment c domain; EP, electroporation; GITR, glucocorticoid-induced tumor necrosis factor receptor family-related genes; HER2, Her2/neu; HSP70, heat shock protein 70; IFNs, interferons; IRF, interferon regulatory factor; Id, idiotype; MHC, major histocompatibility complex; Mam-A, Mammaglobin-A; NHP, non-human primate; PAP, Prostatic acid phosphatase; PMED, particle mediated epidermal delivery; PSMA, prostate-specific membrane antigen; SCT, single-chain trimer; STING, stimulator of interferon genes; TAAs, tumor-associated antigens; TBK1, Tank-binding kinase 1; TLRs, Toll-like receptors; TT, tetanus toxin; Trp2, tyrosinase related protein 2; cellular immune response; hTERT, human telomerase reverse transcriptase; humoral immune response; immune tolerance; phTERT, optimized full-length hTERT; tumor antigens; vaccine delivery.