Clinical Application of Plasmid-Based Cancer Vaccines

Decades of work on DNA-based cancer vaccination has produced numerous clinical candidates, most targeting single tumor-associated antigens, a few targeting multiple antigens or epitopes, and virtually all predominantly aimed at the induction of CD8⁺ cytotoxic T cells. Clinical trials in melanoma, prostate, breast, colorectal, and cervical carcinomas reporting results in the past few years are herein reviewed. Clinical and immunological responses were generally small and detected in only a minority of patients. High doses, extended immunization periods, and multifaceted platforms have modestly improved immunogenicity. Appreciating the important role polyfunctional CD4⁺ helper T cells play in tumor rejection, and using recent advances in epitope mapping and informatics, a new generation of DNA-based vaccines targeting CD4⁺ epitopes that are both tumor reactive and bind multiple MHC class II haplotypes are now entering clinical trials. With such an empirical approach, DNA-based vaccines may be poised to become potent weapons in the armamentarium against cancer.