Vaccination with ant-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity

✍ Scribed by 12 Hirotsugu Uemura; Antonius J. M. C. Beniers; Eigoro Okajima; Frans M. J. Debruyne; Egbert Oosterwijk

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 830 KB
• Volume: 58
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910580418

✦ Synopsis

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Abl), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH3 I, 44.5 I, 7 I, 82 and 9 I) demonstrated specificity for the combining site of Ab I, and appeared to recognize 2 partly overlapping idiotopes on Abl. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab I (Ab I '), as shown by competitive Ab I -antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab I binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-9 Iimmunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH9 I treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.