DNA vaccines to attack cancer: Strategies for improving immunogenicity and efficacy.

DNA vaccination represents a smart and promising approach to cancer immunotherapy. DNA vaccines for cancer immunotherapy are designed to deliver one or several genes encoding tumor antigens, thereby eliciting or augmenting antigen-specific immune responses against antigens that play a central role in tumor initiation, progression and metastasis. Vaccine efficacy can be significantly improved by implementing strategies for enhancing antigen presentation and immunogenicity, such as new delivery systems, addition of molecular adjuvants and immunostimulatory signals, optimized prime-boost strategies or blockade of immune checkpoints. Taken into consideration that innate immune responses are important in the induction and enhancement of antigen-specific adaptive responses, manipulations that integrate these approaches in the vaccine design can achieve activation of protective adaptive immune responses, thereby overcoming the self-tolerance towards many tumor antigens. Such approaches are employed in a number of clinical trials for DNA cancer immunotherapy and hold promise for prophylactic and therapeutic vaccine development. In this context, strategies that improve immunogenicity and enhance the efficacy of DNA vaccines for cancer immunotherapy are discussed.