| Abstract: | Foreign and self endogenous proteins can be processed and presented as peptides bound to class I and II MHC to CD8 or CD4-positive T cells. In the case of mutant tumor suppressor proteins, proteosomal processing of the mutant protein could occur either in the tumor cell or in an antigen-presenting cell to generate a variety of peptides that can be transported into the endoplasmic reticulum and loaded on the MHC. These peptides may induce tumor suppressor specific T cells in the presence of sufficient T help and costimulation. In human cancer, p53 is frequently found to be both somatically mutant and overexpressed. We and others are currently investigating the potential of peptide-induced cellular immunotherapy to induce cytotoxic T cells to peptides containing point mutant p53, or other oncogene products, thus potentially inducing tumor-specific cellular immunity. There are many potential prerequisites for successful immunotherapeutic targeting of intracellular antigens such as p53, including: (1) the protein must have a sufficient expression level; (2) it should be a candidate for proteolytic degradation and transport into the ER; (3) the tumor-specific epitope must have adequate affinity to the corresponding MHC restriction element; (4) the MHC complex must be expressed at sufficient levels on the cell surface to make the tumor-specific epitope accessible to T cells; and (5) the method of therapeutic immunization must effectively induce oncopeptide-specific cytotoxic T lymphocytes. |
