TY - JOUR
T1 - Immunogenicity in rabbits and mice of an antibody-chelate conjugate
T2 - Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent
AU - Watanabe, Naoto
AU - Goodwin, David A.
AU - Meares, Claude F.
AU - McTigue, Maureen
AU - Chaovapong, Warak
AU - Ransone, Charles McK
AU - Renn, Oliver
PY - 1994/2/15
Y1 - 1994/2/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8313361
AN - SCOPUS:0028350986
VL - 54
SP - 1049
EP - 1054
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 4
ER -