title: Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity.
abstract: Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Latzka
authors.forename: Sonja
authors.initials: S
authors.lastname: Gaier
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Hofstetter
authors.forename: Nina
authors.initials: N
authors.lastname: Balazs
authors.forename: Ursula
authors.initials: U
authors.lastname: Smole
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Heimo
authors.initials: H
authors.lastname: Breiteneder
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D019151:Peptide Library; D011817:Rabbits; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D019151:Peptide Library; D000099216:Chondroitin Sulfate Proteoglycan 4