Comparison of Cellular Immunotherapies and Anti-CD3 in the Treatment of MCA-38-LD Experimental Hepatic Metastases in C57BL/6 Mice

An experimental model of hepatic metastases in C57BL/6 mice was used to compare the antitumor effects of lymphokine-activated killer (LAK) cells, anti-CD3-activated T-cells (ATQ, and anti-CD3 alone. Liver metastases were produced by in vivo passage of MCA-38-LD adenocarcinoma via the ileocolic vein. LAK cells and ATC were generated by 3-day in vitro incubation of spleen cells in interleukin 2 and anti-CD3, respectively. Percentage of tumor volume in livers was determined with a morphometric technique. With less than therapeutic LAK cell doses (0.5-1.0 × 107 cells), no effect was seen in mean (+SE, - SE) percentage of tumor volume of control [23.3 (293, 18.5)] compared to LAK cell-treated [21.6 (293,15.9)] animals. The same number of ATC significantly reduced the mean percentage of tumor volume [2.7 (4.7,1.4)] (P < 0.005). High dose interleukin 2 also significantly decreased tumor volume. More strikingly, a single dose of anti-CD3 alone had a beneficial effect on mean percentage of tumor volume when given i.p. [1.0 (1.9, 0.4)] or i.v. [1.2 (1.7,0.7)] (P < 0.0003). A total of 33% of anti-CD3-treated mice had no detectable liver metastases. In 5,Cr release assays, the cytotoxicity of ATC was shown to be partially mediated by nylon wool-adherent accessory cells. The effectiveness of anti-CD3 in this immunotherapy model suggests that a similar approach may be taken to immunotherapy of human malignancies, without the requirements for in v/fro-generated killer cells or exogenously administered interleukin 2.