For much of 2020, focus has been on the development of a vaccine against SARS-CoV-2, the cause of COVID-19. However, vaccine research extends beyond trying to prevent infectious diseases and is also being studied as a tool in the prevention and management on oncological illnesses. According to Clinicaltrials.gov, as of December 2020, there are currently 28 active clinical trials studying the potential efficacy of vaccines in ovarian cancer (OC).

A recent paper highlights the various vaccination mechanisms being studied in the prevention and management of OC. These strategies can be divided into four types: dendritic cell (DC) vaccines, cancer testis antigen (CTA) vaccines, protein/peptide-based vaccines, and recombinant viral vaccines.

DCs are antigen-presenting cells that act as messengers between the innate and adaptive immune system. They do this by processing antigenic material and presenting it on the cell surface to T-cells. In the case of peptide-loaded DCs, these are pulsed with recombinant peptides prior to reinfusion; these peptides include HER (human epidermal growth factor receptor)-2/neu-derived protein, mannan-MUC1 (Mucin 1, cell surface–associated) fusion protein, WT1 (Wilms’ Tumor Gene 1) peptide, rTERT (human telomerase reverse transcriptase) peptide, and PADRE (pan DR epitope) peptide, or neoantigen peptide.

The efficacy of the vaccine may be enhanced by prior administration of low-dose cyclophosphamide. In some cases, DC vaccines are utilized in conjunction with an electrical field that is applied to cells to increase permeability of the cell membrane (i.e., electroporated) to mRNA. DC vaccines may also be whole-tumor lysate–loaded, which indicates that whole tumor cells are utilized as an antigenic source. These produce a variety of antigens associated with a specific tumor. Incorporating neoepitopes, which are major histocompatibility complex bounded proteins that result from tumor-specific mutations, can trigger a T-cell response to the cancer.

A particularly promising technique is the development of personalized vaccines using autologous tumor lysate–loaded DCs and tumor antigen–matched tumor cell lysates; this strategy has shown benefit in recurrent OC.

While CTA expression is restricted to male germ cells in healthy individuals, there is aberrant expression in tumor cells. One of these immunogenic tumor antigens is NY-ESO (New York esophageal squamous cell carcinoma)-1, which is expressed in up to 40% of OC patients. It is thought that NY-ESO affects epigenetic modulation via DNA methylation. Vaccination with NY-ESO-1–derived peptide ESO157-170 has resulted in a durable CD4+ and CD8+ T-cell response in OC in early clinical trials.

The third type of OC vaccine being studied is protein or peptide-based and utilizes defined tumor-associated antigens along with adjuvants. This type of vaccine also involves DC but more indirectly. In this type of vaccine, tumor-associated antigens are processed and presented to T-cells by DC. A common protein, tumor-suppressor protein p53, is overexpressed in OC with up to 25% of patients having antibodies against this protein, but studies to date have not been very successful. Other protein targets of this vaccine include HER-2/neu, WT1, CA(cancer antigen)125, and cytokine Flt (Fms-like tyrosine kinase )3 ligand.

CA125-targeted vaccines have shown some success, although in general, there has been a lack of objective response seen with this type of vaccine. Another strategy employed has been a personalized approach with the selection of antigen based on pre-existing host immunity. While this has met with some early success, the benefit does not appear to be sustained.

Recombinant viral vaccines are the fourth type of immunizations being studied for OC. Viral vectors are engineered to express multiple cancer antigens. Among the viral vectors utilized are recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-N-ESO-1 (rF-NY-ESO-1) in patients with NY-ESO–expressing tumors. A modest immunogenic response characterized by an increase in CD4+ and CD8+ T-cell has been observed. PANVAC is a recombinant poxviral vaccine that contains carcinoembryonic antigen (CEA) and MUC-1 transgenes along with three costimulatory molecules that is also being studied.

While the benefit seen with OC vaccines to date has not been overly impressive, perhaps lessons learned from the warp speed in which COVID-19 vaccines have been developed may be applied in the fight against OC. As immunizers and vanguards of public health, specialty and other pharmacists need to keep abreast of the latest vaccine developments.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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