Antibody-targeted lymphokine-activated killer cells inhibit liver micrometastases in severe combined immunodeficient mice.

Abstract

Animal models for hepatic metastases can facilitate the investigation of lymphokine-activated killer (LAK) cell-based immunotherapy. The aim of this study was to investigate the efficacy of ccM4 antibody-targeted LAK cells in inhibiting hepatic micrometastases. Hepatic micrometastases were generated after the intrasplenic injection of HM7 colon carcinoma cells. TAG72 expression was detected in these hepatic micrometastases using ccM4 antibody. The ccM4 antibody was conjugated onto LAK cells by treatment with 17.5% polyethylene glycol 8000. After the intrasplenic injection of HM7 cells, severe combined 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 micrograms ccM4 and IL-2 (group ii), LAK cells plus IL-2 (group iii), IL-2 alone (group iv), or only phosphate-buffered saline (group v). The ccM4-LAK cells retained cytolytic activity 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). These results show that ccM4 antibody-targeted LAK cells significantly inhibited tumor growth in vivo; thus, they can be potentially useful in treatment of hepatic micrometastases.