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Development of a Novel Methodology for Improving CTL Recognition of Prostate Specific Antigen (PSA) for the Immunotherapy of Prostate Cancer

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Annual rept. 1 Mar 2000-28 Feb 2001

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The major goal of the proposed research is to develop a novel methodology for improving T cell epitopes. The underlying hypothesis is that T cells capable of recognizing tumor-associated antigens TAA are present but often difficult to activate. However, once activated such T cells might be effective against tumors due to the less stringent triggering requirements of mature effectors. We proposed to develop a novel bacterial expression system for modifying and screening the epitopes of PSA, a known TAA. In the current year we have demonstrated the system devised can discriminate peptides with known differences in their ability to stimulate T cells. Further, we have developed a suitable means for mutagenizing each position in a target peptide and a library encoding altered peptides has been constructed and characterized. An initial screen of this library identified an altered peptide ligand that appears approximately 40 fold better able to stimulate a PSA reactive hybridoma. The findings obtained support the hypothesis that altered peptide ligands can be discovered using the novel methodology that we are developing. The studies to date have established proof of principle that this method can be used to improve T cell epitopes.

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  • Biochemistry
  • Medicine and Medical Research

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