title: Idiotypic-anti-idiotypic complexes and their in vivo metabolism.
abstract: BACKGROUND
  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, alphaTS1, were studied.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 alphaTS1 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.
  
  
  CONCLUSIONS
  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/alphaTS1 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.
authors.affiliation: Department of Immunology, Umeå University, Umeå, Sweden. amanda.johansson@climi.umu.se
authors.forename: Amanda
authors.initials: A
authors.lastname: Johansson
authors.forename: Ann
authors.initials: A
authors.lastname: Erlandsson
authors.forename: David
authors.initials: D
authors.lastname: Eriksson
authors.forename: Anders
authors.initials: A
authors.lastname: Ullén
authors.forename: Patrik
authors.initials: P
authors.lastname: Holm
authors.forename: Birgitta E
authors.initials: BE
authors.lastname: Sundström
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Roux
authors.forename: Torgny
authors.initials: T
authors.lastname: Stigbrand
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007167:Immunotherapy / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D009928:Organ Specificity; D014018:Tissue Distribution
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex