Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization.
Bottom Line: In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody.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.
Affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.Show MeSH
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Mentions: To elucidate the structural similarity between the mimotope-induced rFabs and parental HBJ127, we sequenced and compared the variable heavy (VH) and variable light (VL) domains of A18, B3, and C17, respectively. These sequence data have been submitted to the DDBJ/EMBL/GenBank databases under accession numbers AB773873-4 (A18), AB773877-8 (B3), AB773881-2 (C17), respectively. The deduced amino acid sequences of the three clones are shown in Figure 4. In each clone, only a single mutation was found in the FR1 region of the VH domain (99% identical to HBJ127 VH). In contrast, multiple mutations were found mainly in FR regions of VL domain (90–95% identical to HBJ127 VL). As for the complementarity determining region (CDR) sequences, HCDR1-3 and LCDR1-2 were identical to those of HBJ127. Only a single amino acid difference (Thr to Ser) was found in LCDR3. This mutation may not influence the function of rFabs because of their comparable bioactivities to HBJ127. The gene usage and structural homologies between three clones and the parent antibody is shown in Table 4. The VH of the three clones were derived from VHQ52.a5.13, and the VL from IgVk8-30. VH (AB056115) and VL (AB056116) of HBJ127 are also derived from the same germline. From these results, the VH and VL of selected clones were considered to be almost identical to those of HBJ127. We confirmed that linear and cyclic mimotope peptides could induce antibodies structurally equivalent to parental HBJ127.
Affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.