Tumor-specific genetically engineered murine/human chimeric monoclonal antibody.

Murine variable and human constant region exons were fused to produce "chimeric" immunoglobulin gamma and kappa genes. These constructs were cotransfected into murine myeloma cells which then produced and secreted intact, functional antibody. Cells secreting the chimeric antibody were introduced into mice. The engineered immunoglobulin was subsequently harvested from ascites fluid and was purified by affinity chromatography. Its immunological properties were compared to those of the parental murine monoclonal (B6.2), which exhibits specificity for human breast, lung, and colon carcinoma cells. Competitive binding, immunofluorescent cell staining, and analysis of immunoprecipitated antigen gave similar results for the chimeric and murine B6.2. The biodistribution of chimeric and murine B6.2 after injection into mice bearing human tumors was found to be identical. These results suggest that murine/human chimeric antibodies may be viable clinical replacements for murine monoclonals with the potential for better immunological tolerance and pharmacological efficacy.