Open AccessIdentification of anti‐ CD 98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization
Author(s) -
Saito Misa,
Kondo Masahiro,
Ohshima Motohiro,
Deguchi Kazuki,
Hayashi Hideki,
Inoue Kazuyuki,
Tsuji Daiki,
Masuko Takashi,
Itoh Kunihiko
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12365
Subject(s) - mimotope , epitope , antibody , phage display , immunization , adjuvant , antigen , panning (audio) , biology , monoclonal antibody , peptide library , microbiology and biotechnology , virology , immunology , peptide sequence , biochemistry , paleontology , zoom , gene , lens (geology)
A mimotope is an antibody‐epitope‐mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody‐derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor‐suppressing anti‐CD98 heavy chain mA b, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98‐expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope‐immunized mouse spleen‐derived antibody Fab library showed that HeLa cell‐reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen‐reactive Fab clones represented an undetectable minor population in mimotope‐induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co‐administration of adjuvant compounds such as T‐cell epitope peptides and Toll‐like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone.