Immune monitoring of cancer vaccines. Report on a workshop held at the 9th NCI-EORTC Symposium on New Drugs in Cancer Therapy.

Both antibody-mediated and cell-mediated immuno-logic responses may play a role in prevention and treatment of neoplastic disease. Passive transfer of mono-clonal antibodies or activated lymphocytes have produced tumor regression in animal models and in patients with advanced malignancies. However, these approaches are invariably expensive and often cumbersome , and efficacy has been limited. The identification of many tumor-associated or tumor-specific antigens, and new technologies for immunization, present the opportunity to induce anti-tumor immunologic responses in vivo, perhaps with greater efficacy and less expense. For these reasons, substantial resources are currently being devoted to the development of cancer vaccines. The relative anti-tumor efficacy of antibody versus cell-mediated immune responses is not yet known, and perhaps both contribute to the anti-cancer immune response. However, in the past 5 years, the great majority of cancer vaccines entering into clinical trials have been designed to induce cell-mediated immune responses, based on several key developments in the field of cancer immunology, including: 1) the demonstration that immunotherapies, including cancer vaccines, have anti-tumor activity both in animal models and in patients; 2) the recognition of the critical role that T-cells play in these anti-cancer immune responses; 3) the recognition that antigens recognized by T-cells are actually peptide fragments of intracellular proteins that are transported to the endoplasmic reticulum, bound to MHC molecules , and then carried to the cell surface; 4) the recognition that these tumor antigens can be derived from normal proteins with limited normal tissue expression , or from proteins expressed only in tumor, such as mutated oncogenes and viral proteins; 5) the demonstration that these tumor antigens can be shared (expressed by tumors from different patients); and 6) the development of techniques to clone and manipulate these shared antigens to generate defined antigen vaccines. Another key development that has created substantial new interest in cancer vaccines has been the ease with which genes can be introduced into cancer cells to modulate their immunogenicity, in particular genes that express cytokines or other signals important in the presentation of antigen to, and activation of, T-cells. These techniques have allowed the generation of immunogenic cancer vaccines from the patient's own tumor, or from continuously maintained allogeneic cancer cell lines that express shared tumor antigens. In the case where autologous tumor is used as the immunizing preparation, the actual tumor rejection antigen or antigens need not be known. Although several cancer vaccines have been shown to induce …