In the past few years, a number of CTL-defined human tumor peptides have been identified, and attempts are being made for their clinical application. Consequently, preclinical CTL-defined peptide vaccine models are urgently needed to provide insights that might be translated into clinical applications. The Meth A sarcoma is one of the best studied murine tumors, and it is extremely lethal unless protective immunity is induced. A CD8+,H-2Kd-restricted anti-Meth A CTL line has been isolated, and shown by adoptive transfer capable of eradicating Meth A lung metastases. This result confirms the functional role of the epitope in tumor rejection. We have also shown that this epitope is derived from Meth A gp110, a glycoprotein with proven tumor rejection-inducing activity. Independently, a fraction of H-2Kd-associated Meth A peptides was shown to contain the CTL-defined epitope. We are currently using mass spectral (MS) analysis of this peptide fraction as well as information obtained from the isolation and sequence analysis of cDNA encoding Meth A gp110 to identify the CTL-defined Meth A epitope. A critical aspect of peptide-based vaccine development is identification of adjuvants, chemical or cellular, which permit induction of anti- peptide CTL. We have modified published methods for generating bone marrow(BM)derived dendritic cells (DC), which has permitted us to demonstrate the efficacy of peptide-pulsed DC vaccines in two, well- characterized CTL-defined peptide models. In a human papilloma virus type16 E7-peptide model, we have also demonstrated the beneficial effect of administration of E7-pulsed DC on mice bearing 14-day old, locally growing tumors. The evidence of the expression in some human tumors of the human counterpart of Meth A gp110 points to the direct extension of our analysis of Meth A gp110 to clinical studies, and the potentially broad and clinically relevant aspects of our efforts to identify the CTL- defined tumor antigens of the chemically induced BALB/c Meth A and CMS4 sarcomas.
