Treatment Combinations with DNA Vaccines for the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) is a challenging disease to treat, with poor outcomes for patients. One antitumor vaccine, sipuleucel-T, has been approved as a treatment for mCRPC. DNA vaccines are another form of immunotherapy under investigation. DNA immunizations elicit antigen-specific T cells that cause tumor cell lysis, which should translate to meaningful clinical responses. They are easily amenable to design alterations, scalable for large-scale manufacturing, and thermo-stable for easy transport and distribution. Hence, they offer advantages over other vaccine formulations. However, clinical trials with DNA vaccines as a monotherapy have shown only modest clinical effects against tumors. Standard therapies for CRPC including androgen-targeted therapies, radiation therapy and chemotherapy all have immunomodulatory effects, which combined with immunotherapies such as DNA vaccines, could potentially improve treatment. In addition, many investigational drugs are being developed which can augment antitumor immunity, and together with DNA vaccines can further enhance antitumor responses in preclinical models. We reviewed the literature available prior to July 2020 exploring the use of DNA vaccines in the treatment of prostate cancer. We also examined various approved and experimental therapies that could be combined with DNA vaccines to potentially improve their antitumor efficacy as treatments for mCRPC.

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

“…DNA vaccines serve as vehicles for in vivo transfection and antigen production. They consist of a plasmid DNA that encodes the antigen of interest under the control of a eukaryotic promoter [ 118 ]. To date, most DNA vaccines are focusing on antigens specific for PCa (e.g., PAP, PSA, or AR), while targeting of other tumor-specific mutation-associated neoantigens is challenging due to the rather low TMB of PCa.…”

Cancer immunotherapy: A comprehensive appraisal of its modes of application (Review)

“…In addition, the use of DNA vaccines is supported by the fact that intrinsic unmethylated CpG islands in the bacterial plasmid function as an adjuvant, thus stimulating the immune response to the vaccine (92). To determine the most effective combination of treatments and DNA vaccines, assessment of the tumor microenvironment as well as cells involved in the immunosuppressive behavior in that niche should be performed (93).…”

“…The advantages of using DNA vaccines include their low cost, ability to elicit antigen-specific immune responses, easy sequence alteration, large-scale production and storage (93). In addition, DNA vaccines are not infectious and do not cause diseases or elicit immune responses in individuals of a specific MHC class (93). Therefore, in contrast to personalized vaccines, DNA vaccines may be considered versatile (93).…”

“…In addition, DNA vaccines are not infectious and do not cause diseases or elicit immune responses in individuals of a specific MHC class (93). Therefore, in contrast to personalized vaccines, DNA vaccines may be considered versatile (93). Finally, as these antigens are expressed in the cells, they undergo post-translational modifications that form proteins similar to the host proteins, which ensures appropriate immune presentation (94).…”

Construction of an Effective Delivery System for DNA Vaccines Using Biodegradable Polylactic Acid Based Microspheres

“…(1) the potential to induce a broad immune response without the risks observed using replicating microorganisms [1] ; (2) the ability to simultaneously stimulate humoral and cellular immunity [2] ; (3) the process of purifying plasmid DNA is simple, inexpensive, and suitable for mass production [3] ; (4) DNA molecules are stable, therefore easy to transport and preserve [4] ; and (5) by simply mixing multiple plasmid DNA samples, antigens with similar biochemical properties can be combined to form a multivalent vaccine [5] . Based on these advantages, DNA vaccines may be substitutes for traditional vaccines and may have a wide range of applications in the treatment of infectious diseases in humans and animals [6] .…”