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Internal image anti-idiotype antibodies related to renal-cell carcinoma-associated antigen G250

✍ Scribed by H. Uemura; E. Okajima; F. M. J. Debruyne; E. Oosterwijk


Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
763 KB
Volume
56
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

The potential usefulness of internal‐image anti‐idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor‐associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal‐cell carcinoma‐associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western‐blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross‐blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group 1; NUH31, 51,71, group 2; NUH44, 82, 91). However, cross‐reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen‐positive cell lysates, but not with antigen‐negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti‐anti‐idiotype antibodies resembling MAbG250 (Ab1). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal‐cell carcinoma.


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## Abstract We previously identified an HLA‐A2.1‐restricted epitope within the RCC‐associated antigen G250 that is recognized by CTLs. Using DCs of healthy individuals, which were loaded with overlapping 20 mer G250‐derived peptides, we here report the induction of CD4^+^ T cells that recognize the