ABSTRACT
Because the immune system has the capacity to recognize and in many cases destroy tumor cells, significant efforts are being devoted to the development of immune-based therapies for cancer. Both cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) have been shown to react with antigens expressed by tumor cells and as a result, estab lish protective and therapeutic effects. Since CTL and HTL recognize antigens in the form of peptide complexes with major histocompatibility complex (MHC) surface molecules (HLA in humans), it is necessary to identify the nature of tumor-derived peptides that can elicit T-cell responses capable of inhibiting tumor-cell growth. The overall objective of our work is to identify peptides derived from sequences of several known tumor-associated antigens (TAA) that are capable of stimulating CTL and HTL against tumor cells. The amino acid sequences of TAA are screened for the presence of peptides containing MHC binding motifs. Corre sponding peptides are then synthesized and tested for their capacity to elicit in vitro T-cell responses to tumor cells and corresponding TAA as a final proof that they truly represent T-cell epitopes. As a consequence of these studies, the identified tumor-reactive T-cell epitopes can be developed into therapeutic compounds to treat commonly found epithelial cancers (breast, gastrointestinal and lung). The remaining challenges are how to select the most appropriate mode of vaccination and how to evaluate the effectiveness of immunotherapy in the cancer setting.
