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Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity.

Latzka, Julia and Gaier, Sonja and Hofstetter, Gerlinde and Balazs, Nina and Smole, Ursula and Ferrone, Soldano and Scheiner, Otto and Breiteneder, Heimo and Pehamberger, Hubert and Wagner, Stefan (2011) Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity. PLoS One, 6 (5). e19383 - ?.

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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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Latzka, Julia
Gaier, Sonja
Hofstetter, Gerlinde
Balazs, Nina
Smole, Ursula
Ferrone, Soldano
Scheiner, Otto
Breiteneder, Heimo
Pehamberger, Hubert
Wagner, Stefan
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHerlyn, MeenhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 28 March 2011
Date Type: Acceptance
Journal or Publication Title: PLoS One
Volume: 6
Number: 5
Page Range: e19383 - ?
DOI or Unique Handle: 10.1371/journal.pone.0019383
Schools and Programs: School of Medicine > Immunology
School of Medicine > Pathology
School of Medicine > Surgery
Refereed: Yes
Uncontrolled Keywords: Animals, Antibodies, Neoplasm, Antigens, Neoplasm, Cell Line, Tumor, Enzyme-Linked Immunosorbent Assay, Epitopes, Flow Cytometry, Humans, Immunohistochemistry, Mice, Peptide Library, Rabbits
MeSH Headings: Animals; Antibodies, Neoplasm--immunology; Antigens, Neoplasm--immunology; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Epitopes--immunology; Flow Cytometry; Humans; Immunohistochemistry; Mice; Peptide Library; Rabbits
Other ID: NLM PMC3089623
PubMed Central ID: PMC3089623
PubMed ID: 21573118
Date Deposited: 29 Aug 2012 21:10
Last Modified: 20 Dec 2018 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/13831

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