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Idiotypic–anti-idiotypic complexes and their in vivo metabolism
Article first published online: 12 FEB 2002
Copyright © 2002 American Cancer Society
Supplement: Eighth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer
Volume 94, Issue Supplement 4, pages 1306–1313, 15 February 2002
How to Cite
Johansson, A., Erlandsson, A., Eriksson, D., Ullén, A., Holm, P., Sundström, B. E., Roux, K. H. and Stigbrand, T. (2002), Idiotypic–anti-idiotypic complexes and their in vivo metabolism. Cancer, 94: 1306–1313. doi: 10.1002/cncr.10301
- Issue published online: 12 FEB 2002
- Article first published online: 12 FEB 2002
- Manuscript Accepted: 14 NOV 2001
- Manuscript Received: 31 OCT 2001
- Swedish Cancer Research Council. Grant Number: 1387
- Lions Foundation in Umeå, Sweden
- University of Umeå, Sweden
- National Institutes of Health. Grant Number: R21 AI 144291
- immune complex;
Different strategies can be used to improve the tumor:non-tumor ratio of radiolabeled antibodies in immunotargeting. One approach is to use secondary antibodies to clear out redundant, circulating primary antibodies. In the current study, the in vitro complex formation and in vivo clearing capabilities and metabolism of the monoclonal antibody TS1 and its monoclonal anti-idiotype, αTS1, were studied.
Complex formation studies were performed using polyacrylamide gel electrophoresis (PAGE), gel permeation chromatography, and electron microscopy. The clearance and metabolism of the complexes were studied in nude mice.
PAGE and gel permeation chromatography showed that more than 70% of the antibodies formed complexes. The electron microscopy studies revealed that the complexes formed between TS1 and αTS1 are mainly ring-shaped (66.6–73.4%), comprising 4 to > 8 antibodies. These rings consist of equal numbers of idiotype and anti-idiotype. The most commonly observed complexes were tetrameric rings (26.8–40.5%), hexameric rings (10.7–11.9%), and rings containing more than eight monoclonal antibodies (6.6–14-4%). The in vivo study illustrated that within 24 hours 80% of the total nuclide content had been degraded and excreted via the urine, compared with 25% for similarly treated mice that did not receive any anti-idiotype.
Interestingly, the electron microscopy study demonstrated that dimers were rare (0.4–1.2%), probably reflecting a location of epitopes incompatible with tight, sterically constrained dimeric interactions; insufficient flexibility of the immunoglobulin G1 subtype hinge regions; or both. The anti-idiotypic clearing mechanisms proved efficient in nude mice. In vivo metabolic studies indicate that the accumulation and degradation of TS1/αTS1 immune complexes, to a large extent, take place in the liver, where a substantial amount was detected as soon as 1 hour after anti-idiotype injection. Cancer 2002;94:1306–13. © 2002 American Cancer Society.