LOCALIZATION OF COMPLEMENT-FIXING CYTOTOXIC MONOCLONAL-ANTIBODIES TO SUBCUTANEOUS TUMORS AND LIVER METASTASES IN A SYNGENEIC IMMUNOCOMPETENT RAT COLON-CARCINOMA MODEL

To study the immune effects of complement-fixing cytotoxic monoclonal antibodies (mAbs) in a syngeneic immunocompetent animal model, mouse m Abs reactive with the transplantable rat colon carcinoma K12/TRb were generated. This system was used in part because rats have a complement system superior to that of mice. Seven murine IgG mAbs that reacted s trongly with cell surface determinants of the K12/TRb rat colon carcin oma cell line were produced by immunizing MRL/Mp-1pr/1pr autoimmune mi ce, known to produce an increased amount of complement-fixing IgG2a an d IgG3 immune cytotoxic antibodies, with K12/TRb cells. These mAbs wer e screened for their specificity of reaction, and two of these mAbs we re extensively tested for their ability to lyse cells in vitro and loc alize to K12/TRb tumors in syngeneic BD IX rats. IgG2a mAbs 27-3 and 6 1-5 were able to mediate both complement and lymphocyte cytotoxicity i n vitro and localize to subcutaneous tumors and liver metastases in th is immunocompetent rat model.