Cancer Vaccines, Adjuvants, and Delivery Systems

Abstract

Vaccination was first pioneered in the 18th century by Edward Jenner and eventually led to the development of the smallpox vaccine and subsequently the eradication of smallpox. The impact of vaccination to prevent infectious diseases has been outstanding with many infections being prevented and a significant decrease in mortality worldwide. Cancer vaccines aim to clear active disease instead of aiming to prevent disease, the only exception being the recently approved vaccine that prevents cancers caused by the Human Papillomavirus. The development of therapeutic cancer vaccines has been disappointing with many early cancer vaccines that showed promise in preclinical models often failing to translate into efficacy in the clinic. In this review we provide an overview of the current vaccine platforms, adjuvants and delivery systems that are currently being investigated or have been approved. With the advent of immune checkpoint inhibitors, we also review the potential of these to be used with cancer vaccines to improve efficacy and help to overcome the immune suppressive tumor microenvironment.

Keywords: DNA vaccine; adjuvant; cancer; peptide vaccine; vaccine.

Figure 1

Schematic of the citrullination or deamidation of arginine.

Figure 2

During stress induced autophagy and in the presence of inflammation citrullinated peptides can be presented on major histocompatibility complex (MHC) class II molecules for recognition by CD4+ T cells. During inflammation many cytokines are produced, the majority are proinflammatory that result in the upregulation of MHC class II expression that then activates CD4+ T cells. Primed killer CD4 T cells enter the tumor and are reactivated by APCs presenting citrullinated peptides from tumors allowing recognition and lysis by the killer CD4 T cells.

Figure 3

Neoantigens currently in clinical trial. According to clinicaltrials.gov (as of 23^rd September 2020) there are currently 33 clinical trials recruiting that target neoantigens.

Figure 4

Survival of HHDII mice challenged with 5 x10⁴ tumor cells and immunized with SCIB2 and anti-PD-1 antibody alone or in combination. Control vs SCIB2 (*p = 0.037); Control vs anti-PD-1 antibody (p = 0.111); Control vs SCIB2 and anti-PD-1 antibody (***p = 0.0003); SCIB2 vs SCIB2 and anti-PD-1 (* = 0.0177); anti-PD-1 antibody vs SCIB2 and anti-PD-1 (*P = 0.0177). Lack of survival was defined as tumor size > 528 mm³. Each curve represents at least 10 mice per group.