A chimeric mouse/human anti-IL-2 receptor antibody with enhanced biological activities.
A chimeric mouse/human MAb against the human p55 IL-2R was constructed from Ig genes isolated from a mouse hybridoma cell line, designated AHT107. AHT107 binds to a different epitope on p55 than IL-2, and similar to observations made for other rodent anti-IL-2R antibodies that do not recognize the same or spatially related epitope as IL-2, murine AHT107 did not efficiently inhibit proliferation of T-lymphocytes in mitogen and MLR PBMC stimulation assays. In contrast, the chimeric AHT107 antibodies containing a human IgG-1 constant region had substantially more anti-proliferative activity than their murine IgG-I counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in the PBMC cultures. This conclusion was supported by our observation that F(ab')2 generated from the chimeric antibodies did not efficiently inhibit proliferation in the PBMC assays, and the chimeric antibodies did not inhibit proliferation of an antigen specific, IL-2 dependent human T-cell clone stimulated in the absence of PBMC.
Rose
B
B
Molecular Therapeutics, Miles Research Center, W. Haven, CT 06516.
Gillespie
A
A
Wunderlich
D
D
Barbosa
J A
JA
Cahill
K
K
Dzuiba
J
J
Shedd
D
D
Zerler
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D009841:Oligonucleotides; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D004247:DNA