Open AccessChimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells.
Author(s) -
A Y Liu,
Randy Robinson,
Karl Erik Hellström,
Euan Murray,
Chia-Ching Chang,
Ingegerd Hellström
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.10.3439
Subject(s) - antibody , microbiology and biotechnology , cytolysis , biology , antigen , monoclonal antibody , transfection , fusion protein , chimeric gene , complementary dna , cell culture , chemistry , cytotoxicity , immunology , recombinant dna , in vitro , biochemistry , gene , gene expression , genetics
A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C gamma 2a and C kappa, were substituted by the human C gamma 1 and C kappa by recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man.