Translating tumor antigens into cancer vaccines

Abstract

Vaccines represent a strategic successful tool used to prevent or contain diseases with high morbidity and/or mortality. However, while vaccines have proven to be effective in combating pathogenic microorganisms, based on the immune recognition of these foreign antigens, vaccines aimed at inducing effective antitumor activity are still unsatisfactory. Nevertheless, the effectiveness of the two licensed cancer-preventive vaccines targeting tumor-associated viral agents (anti-HBV [hepatitis B virus], to prevent HBV-associated hepatocellular carcinoma, and anti-HPV [human papillomavirus], to prevent HPV-associated cervical carcinoma), along with the recent FDA approval of sipuleucel-T (for the therapeutic treatment of prostate cancer), represents a significant advancement in the field of cancer vaccines and a boost for new studies in the field. Specific active immunotherapies based on anticancer vaccines represent, indeed, a field in continuous evolution and expansion. Significant improvements may result from the selection of the appropriate tumor-specific target antigen (to overcome the peripheral immune tolerance) and/or the development of immunization strategies effective at inducing a protective immune response. This review aims to describe the vast spectrum of tumor antigens and strategies to develop cancer vaccines.

FIG. 1.

Schematic representation of a DC-based vaccine preparation. CD14⁺ monocytes or CD34⁺ hematopoietic progenitors are derived from patients. Different DC subsets are generated in vitro, with distinct specialization in driving adaptive immunity to the Th1 or Th2 response. Mature DCs are loaded with one of the indicated sources of tumor antigens and reinfused in the patient. The most relevant cell markers characterizing the different activation stages of DCs are indicated.