The future of cancer immunotherapy: DNA vaccines leading the way

Immuno-oncology has revolutionized cancer treatment and has opened up new opportunities for developing vaccination methods. DNA-based cancer vaccines have emerged as a promising approach to activating the bodily immune system against cancer. Plasmid DNA immunizations have shown a favorable safety profile and there occurs induction of generalized as well as tailored immune responses in preclinical and early-phase clinical experiments. However, these vaccines have notable limitations in immunogenicity and heterogeneity and these require refinements. DNA vaccine technology has been focusing on improving vaccine efficacy and delivery, with parallel developments in nanoparticle-based delivery systems and gene-editing technologies such as CRISPR/Cas9. This approach has showcased great promise in enhancing and tailoring the immune response to vaccination. Strategies to enhance the efficacy of DNA vaccines include the selection of appropriate antigens, optimizing insertion in a plasmid, and studying combinations of vaccines with conventional strategies and targeted therapies. Combination therapies have attenuated immunosuppressive activities in the tumor microenvironment and enhanced the capability of immune cells. This review provides an overview of the current framework of DNA vaccines in oncology and focuses on novel strategies, including established combination therapies and those still under development.The challenges that oncologists, scientists, and researchers need to overcome to establish DNA vaccines as an avant-garde approach to defeating cancer, are also emphasized. The clinical implications of the immunotherapeutic approaches and the need for predictive biomarkers have also been reviewed upon. We have also tried to extend the role of Neutrophil extracellular traps (NETs) to the DNA vaccines. The clinical implications of the immunotherapeutic approaches have also been reviewed upon. Ultimately, refining and optimizing DNA vaccines will enable harnessing the immune system's natural ability to recognize and eliminate cancer cells, leading the world towards a revolution in cancer cure.