Identification of the Genes Encoding Cancer Antigens: Implications for Cancer Immunotherapy

This chapter focuses on the identification of the genes encoding cancer antigens. The development of new cancer therapies based on stimulating the immune response of the host against a growing malignancy is based on the hypothesis that cancers contain, on their surface, unique antigens that can serve as targets for immune destruction. The validity of this hypothesis was bolstered by the development of immune manipulations that could mediate the rejection of growing cancers in humans and by the identification of T lymphocytes that could specifically recognize cancer cells in vitro. A variety of techniques have been developed that enable the identification of T lymphocytes that selectively recognize tumor antigens. A variety of methods have been used to identify human melanoma antigens recognized by T cells. Approaches to cancer immunotherapy can be divided into active or passive categories. Active immunotherapy involves the direct immunization of cancer patients with cancer antigens in an attempt to boost immune responses against the tumor. Passive immunotherapy refers to the administration of immune reagents, such as immune cells or antibodies with antitumor reactivity, with the goal of directly mediating antitumor responses. The most effective forms of immunization involve the incorporation of genes encoding immunogenic molecules into recombinant bacteria—such as bacillus Calmette-Guerin, Salmonella, or Listeria—or into recombinant viruses—such as vaccinia, fowlpox,or adenovirus. The genes encoding cancer antigens can be expressed either alone or in combination with genes encoding cytokines, costimulatory molecules, or other genes that can enhance the immune response following infection. Many of these approaches to active immunization are being pursued in experimental animal models using model tumor antigens. The availability of the genes encoding human tumor antigens has led to the development of clinical trials in humans with cancer.