Cytokine Gene-Modified Cell-Based Cancer Vaccines

Antitumor immunity was first suggested in animals that reject tumor challenge after immunization with autologous inactivated tumor cells. Later, the discovery of tumor antigens recognized by T-cells strongly reinforced the concept that the tumor can be targeted by the immune system. In 1991, Boon and colleagues described the first human tumor antigen, MAGE-1 , that is expressed in 50–60% of melanomas (1 ). The identification of T-cell-dependent tumor antigens (MAGE family, BAGE , GAGE , HER2/neu , p53 , MART-1 , tyrosinase, HPV , and others) has opened the route of antigen-specific immunotherapy strategies (2 ,3 ). Despite these important advances in tumor immunology, most tumor antigens are still unknown. Until more common tumor-specific antigens have been identified and their prevalence and relevance have been evaluated, the tumor cell itself remains one of the most convenient sources of antigens. Preclinical studies have shown that immunization with modified inactivated tumor cells can generate systemic antitumor immunity in vivo (4 ). Currently, many clinical studies are investigating the safety and efficacy of autologous and allogeneic whole cell-based cancer vaccines (5 ).