The dawn of vaccines for cancer prevention

Abstract

An important role of the immune system is in the surveillance for abnormal or transformed cells, which is known as cancer immunosurveillance. Through this process, the first changes to normal tissue homeostasis caused by infectious or other inflammatory insults can be detected by the immune system through the recognition of antigenic molecules (including tumour antigens) expressed by abnormal cells. However, as they develop, tumour cells can acquire antigenic and other changes that allow them to escape elimination by the immune system. To bias this process towards elimination, immunosurveillance can be improved by the administration of vaccines based on tumour antigens. Therapeutic cancer vaccines have been extensively tested in patients with advanced cancer but have had little clinical success, which has been attributed to the immunosuppressive tumour microenvironment. Thus, the administration of preventive vaccines at pre-malignant stages of the disease holds promise, as they function before tumour-associated immune suppression is established. Accordingly, immunological and clinical studies are yielding impressive results.

An agonistic anti‐Toll‐like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy

“…6,15,16 In this study, we showed that an agonistic anti-TLR4 mAb induces tumour-specific immune responses in mice immunized with a tumourspecific Ag, which enhanced the therapeutic efficacy of the anti-PD-1 mAb. 6,15,16 In this study, we showed that an agonistic anti-TLR4 mAb induces tumour-specific immune responses in mice immunized with a tumourspecific Ag, which enhanced the therapeutic efficacy of the anti-PD-1 mAb.…”

“…This possibility suggests that OVA/anti-TLR4 mAb therapy may be effective against some MHC I-negative tumours. [15][16][17]35 Thus, most tumour Ags expressed exclusively or preferentially by tumours, but not normal tissues, are likely not suitable targets for tumour vaccine therapy. 46 Whereas EG7 and MC38 cells secrete OVA extracellularly, B16F10 cells retain OVA intracellularly because the transfected OVA lacks a signal peptide.…”

“…Indeed, B16F10 tumours can be eradicated by cytotoxic CD8 T-cells in vivo. [15][16][17] The application of next-generation sequencing and bioinformatics has shown that neoantigens produced by mutations in individual tumours are targets of antitumour immunity. The subcellular 0·7 0·9% 17% % Figure 5.…”

“…4,5,10,12 Thus, patients with low-immunogenicity tumours are unlikely to benefit from immune-checkpoint-blocking Abs because I M M U N O L O G Y O R I G I N A L A R T I C L E antitumour immunity is not stimulated and/or due to the immune-evasion mechanism(s) of the tumours. 13,15,16 In contrast to immune-checkpoint blockade, cancer vaccines comprising tumour-associated or -specific antigens (Ags) prime and/or activate antitumour immune cells, such as cytotoxic T-cells. 13,15,16 In contrast to immune-checkpoint blockade, cancer vaccines comprising tumour-associated or -specific antigens (Ags) prime and/or activate antitumour immune cells, such as cytotoxic T-cells.…”

Synthetic, Supramolecular, and Self‐Adjuvanting CD8+ T‐Cell Epitope Vaccine Increases the Therapeutic Antitumor Immunity

“…[32,37] It is better that the immunosuppressive tumoral microenvironment was concurrently inhibited to reduce the escape of cancer cells from the immunosurveillance by the immune system. Commonly, cellular immune response is essential for cancer immunotherapy, and CD8 + effector T cells have to infiltrate the tumor tissue to eliminate tumor cells.…”