Characterization of a human-mouse chimeric antibody reactive with a human melanoma associated antigen.
The data presented demonstrate that a human-murine chimeric antibody has been generated that retains the immunoreactivity and has similar pharmacokinetic properties of its parent murine monoclonal antibody NRML-05. A competitive ELISA assay demonstrated that antigen reactivity of both parent and chimera were nearly identical. In a direct cell binding assay, NRML-05 and chimeric antibodies were immunoreactive, 81% and 83%, respectively. Scatchard Analysis of the antibodies indicate very similar affinities for NRML-05 (4.4 x 10(9) M-1) and chimera (2.7 x 10(9) M-1). Localization of the two antibodies to tumor xenografts in nude mice were very similar in biodistribution studies. The chimeric antibody is not as well recognized by antiglobulin from patients who have responded to non-idiotypic murine antibody determinants. Although this data does not predict how immunogenic a chimera would be in the clinical setting, it does suggest that patients without significant anti-idiotypic antiglobulin response could benefit from second and subsequent administrations with chimeric antibody. Even though anti-idiotypic responses may occur with the chimera, these may be reduced as a result of the presentation of these epitopes on the less immunogenic human constant domains.
Marchitto
K S
KS
NeoRx Corporation, Seattle, Washington 98119.
Kindsvogel
W R
WR
Beaumier
P L
PL
Fine
S K
SK
Gilbert
T
T
Levin
S D
SD
Woodhouse
C S
CS
Morgan
A C
AC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm; D000939:Epitopes / Q000276:immunology; D005813:Genes, Synthetic; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D008545:Melanoma / Q000276:immunology*; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D058950:Melanoma-Specific Antigens; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology*; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D007074:Immunoglobulin G; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011994:Recombinant Proteins