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 mAbs 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 strongly with cell surface determinants of the K12/TRb rat colon carcinoma cell line were produced by immunizing MRL/Mp-1pr/1pr autoimmune mice, known to produce an increased amount of complement-fixing IgG2a and IgG3 immune cytotoxic antibodies, with K12/TRb cells. These mAbs were screened for their specificity of reaction, and two of these mAbs were extensively tested for their ability to lyse cells in vitro and localize to K12/TRb tumors in syngeneic BD IX rats. IgG2a mAbs 27-3 and 61-5 were able to mediate both complement and lymphocyte cytotoxicity in vitro and localize to subcutaneous tumors and liver metastases in this immunocompetent rat model.