Immunogenicity in rabbits and mice of an antibody-chelate conjugate: Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent

Naoto Watanabe, David A. Goodwin, Claude F. Meares, Maureen McTigue, Warak Chaovapong, Charles McK Ransone, Oliver Renn

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The macrocyclic bifunctional chelating agent 2-(p-bromoacetamidobenzyl)- 1,4,7,10-tetraazacyclododecanetetraacetic acid (BAD), forms inert metal complexes ideal for radioimmunotherapy. Kosmas et al. (Cancer Res., 52: 904- 911, 1992) found 2-imminothiolane linker-(S)-BAD monoclonal antibody HMFG1 highly immunogenic in patients. We studied the immunogenicity of (S) and (R) enantiomers of 2-imminothiolane linker-BAD rabbit IgG, monoclonal antibody Lym-1, and Lym-1 2-imminothiolane linker-(S)-bromoacetamidobenzyl-EDTA in 15 rabbits. Five groups of three each were given 0.1, 1.0, or 10 mg of 111In conjugate i.v., blood samples were taken daily for 14 days and biweekly for 70 days, and the plasma T( 1/2 ) was calculated. A drop in plasma 111In at 6- 8 days coincided with the appearance of antibody on enzyme-linked immunosorbent assay. Specific anti-(S)-BAD, anti-(R)-BAD, anti-(S)- bromoacetamidobenzyl-EDTA, and anti-mouse IgG were measured. Rabbit IgG conjugates did not elicit an immune response. Mouse IgG conjugates were immunogenic on the first exposure, with both anti-1,4,7,10- tetraazacylododecane N,N',N'',N'''-tetraacetic acid and anti-mouse responses. Anti-1,4,7,10-tetraazacylododecane N,N',N'',N'''-tetraacetic acid was specific for the (S) or (R) enantiomer, but cross-reaction appeared with reboosting. A second injection of the opposite enantiomer gave a response to that enantiomer. Lym-1 bromoacetamidobenzyl-EDTA produced anti- bromoacetamidobenzyl-EDTA and anti-mouse response.

Original languageEnglish (US)
Pages (from-to)1049-1054
Number of pages6
JournalCancer Research
Volume54
Issue number4
StatePublished - Feb 15 1994

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Immunogenicity in rabbits and mice of an antibody-chelate conjugate: Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent'. Together they form a unique fingerprint.

  • Cite this

    Watanabe, N., Goodwin, D. A., Meares, C. F., McTigue, M., Chaovapong, W., Ransone, C. M., & Renn, O. (1994). Immunogenicity in rabbits and mice of an antibody-chelate conjugate: Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent. Cancer Research, 54(4), 1049-1054.