Tumor Associated Antigenic Peptides in Prostate Cancer

摘要

We had earlier demonstrated the prophylactic and therapeutic efficacy of tumor derived heat shock protein, gp96-peptide complexes. Since this tumor rejection property was specifically mediated by tumor derived and not non-tumor derived gp96-peptide complexes, and that gp96 preparations stripped of its peptides are non-immunogenic, we examined the hypothesis whether prostate cancer associated peptides which may act as tumor rejection antigens can be identified in gp96-peptide complexes utilizing a combinatorial single chain phage display antibody library. We have successfully used combinatorial single chain phage display library (scFv) for the detection of tumor rejection antigens and to define the heterogeneity of cancer antigens in prostate cancer. These novel reagents helped us to characterization of the 170 kDa protein specifically expressed in MAT-LyLu cells that could be a target for immunotherapy. These scFvs were used to identify synthetic peptides that mimic the activity of the tumor rejection antigen gp96. We also demonstrated that a tumor protective immune response can he generated using these synthetic peptides. Our results now confirm that T cell defined epitopes can be recognized by antibodies and that there may exist considerable overlap. In this respect, the existing paradigm was challenged.