ANTIBODY-TARGETED LYMPHOKINE-ACTIVATED KILLER-CELLS INHIBIT LIVER MICROMETASTASES IN SEVERE COMBINED IMMUNODEFICIENT MICE

Background & Aims: Animal models for hepatic metastases can facilitate the investigation of lymphokine-activated killer (LAK) cell-based imm unotherapy, The aim of this study was to investigate the efficacy of c cM4 antibody-targeted LAK cells in inhibiting hepatic micrometastases. Methods: Hepatic micrometastases were generated after the intraspleni c injection of HM7 colon carcinoma cells, TAG72 expression was detecte d in these hepatic micrometastases using ccM4 antibody, The ccM4 antib ody was conjugated onto LAK cells by treatment with 17.5% polyethylene glycol 8000. After the intrasplenic injection of HM7 cells, severe co mbined immunodeficient mice were randomized into five groups (i-v) and received either 10(7) ccM4-LAK cells plus 1000 U interleukin 2 (IL-2; group i), LAK cells plus 50 mu g ccM4 and IL-2 (group ii), LAK cells plus IL-2 (group iii), IL-2 alone (group iv), or only phosphate-buffer ed saline (group v). Results: The ccM4-LAK cells retained cytolytic ac tivity and acquired TAG72-binding reactivity, The results showed that group i had significantly fewer hepatic metastases compared with group ii or group iii (P < 0.05) and even fewer hepatic metastases compared with group iv or group v (P < 0.001). Conclusions: These results show that ccM4 antibody-targeted LAK cells significantly inhibited tumor g rowth in vivo; thus, they can be potentially useful in treatment of he patic micrometastases.