Abstract
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, identification of neoantigens, mutanome studies, designing fusion plasmids, vaccine adjuvant modifications, and co-treatment with immune-checkpoint inhibitors. In this review, we follow a Porter’s analysis analogy, otherwise commonly used in business models, to analyze various immune-forces that determine the potential success and sustainable positive outcomes following DNA vaccination using non-viral tumor associated antigens in treatment against cancer.
Highlights
Advances in immune understanding have enhanced optimism towards DNA-based vaccine therapies against cancer
Pre-clinical murine studies have demonstrated that passive transfer of T-cells from Mam-A vaccinated human leukocyte antigen (HLA)-A2/hCD8 double transgenic mice into a human breast cancer implanted NOD/SCID mouse resulted in significant tumor regression [31,32,33]
Our studies demonstrated that following Mam-A cDNA vaccination, there was an upregulation of tumor lytic CD4+ ICOShi T-cells in Mam-A vaccinated breast cancer patients [34] and induction of antigen specific CD8+ T-cell effector responses [18]
Summary
Advances in immune understanding have enhanced optimism towards DNA-based vaccine therapies against cancer. While the traditional treatment approaches such as tumor resection, radiotherapy, and anti-cancer chemotherapy have shown success in early stage localized tumors, they have only limited role against later staged metastatic malignancies. These standard agents have shown to cause extensive damage to normal tissues leading to hair loss, blood cell destruction, and debilitating side effects such as decreased appetite, hair loss, and immune-suppression. DNA-based vaccines have been developed as a concrete and viable approach and anti-cancer treatment strategy [2]. Major histocompatibility complex; TLR, toll-like receptor; MDSCs, myeloid-derived suppressor cells
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