Epitope-specific antibody response to HT-1080 fibrosarcoma cells by mimotope immunization

Mouse monoclonal antibody (mAb) BCD-F9, which recognizes an unknown antigen found on the surface of many tumor cells, was used to screen a phage displ ay library expressing random peptide decamers. The phage that was selected encoded the unique sequence GRRPGGWWMR, representing the peptide capable of binding to the BCD-F9 mAb, The peptide was synthesized and found to specif ically inhibit the binding of mAb to HT-1080 fibrosarcoma cells. Alanine mu tagenesis of the sequence encoding this peptide indicated that three residu es, PXXWW, were critical for its binding to the BCD-F9 mAb. Polyclonal anti bodies generated by immunization of rabbits with the synthetic peptide GRRP GGWWMR (anti-mimotope antiserum or AM-F9) bound specifically to HT-1080 cel ls and inhibited the binding of the BCD-F9 mAb to these cells, Using an exp erimental animal model in which CD-1 nude mice are inoculated i.v. with HT- 1080 cells, develop lung metastasis, and die within 30 days, we have shown that AM-F9 could significantly prolong the life span of these animals. Our results suggest that a peptide mimotope can potentially be used as a novel immunotherapy to induce a beneficial antitumor response.