Mouse/Human Chimeric Antibodies to a Tumor-Associated Antigen: Biologic Activity of the Four Human IgG Subclasses

摘要: Variable region genes from mouse monoclonal antibody 17-1A (gamma 2a kappa) with specificity for human gastrointestinal malignancies have been paired immunoglobulin constant (for heavy and light chains) to produce mouse/human chimeric molecules (chIgG) each of the four IgG subclasses. Mouse chIgG bound similarly two colon cancer cell lines had comparable binding affinities. The chIgG1 chIgG3 mediated lymphocyte monocyte antibody-dependent cell-mediated cytotoxicity (ADCC) tumor that parent murine 17-1A. chIgG2 chIgG4 were able mediate ADCC but clearly inferior reagents. None antibodies or was complement lysis lines. These studies demonstrate ability all subclass which retain biologic activity. We confirmed preferences Fc receptors subclasses previously determined by monomeric aggregated IgG. data may aid in selection vivo trials.