Augmentation of the antitumor effect of adoptive immunotherapy by in vivo sensitization of EL-4 lymphoma and pre-treatment with sizofiran.

Abstract

The antitumor effects of adoptive immunotherapy using LAK cells treated with sizofiran (SPG) following in vivo antigen sensitization with EL-4 lymphoma (EsLAK), comparing nonsensitized LAK cells (sLAK), were studied in mice with intraperitoneal implantation of EL-4 lymphoma. EL-4 cells treated with Mitomycin C (100 micrograms/ml) were introduced by inoculation into the peritoneum of C57BL/6 mice for antigen sensitization. Four days later, SPG (100 micrograms) was intramuscularly injected. Three days after SPG administration, mononuclear cells obtained from the spleen were prepared for LAK cells (EsLAK). The following results were obtained: 1) The survival period was significantly greater in the sLAK and EsLAK groups than in the control group. The survival period in the EsLAK group was significantly greater than that in the sLAK group. 2) The number of EL-4 cells in the peritoneal exudate cells 11 days postimplantation was lowest in the EsLAK group, and the number of lymphocytes including LGL was largest in the EsLAK group, compared with the sLAK group and the control group. 3) The EsLAK cells showed significantly more enhanced cytotoxic activity against EL-4 than the sLAK cells. 4) Histopathological findings of metastatic lesions of the liver and spleen stained by HE 11 days postimplantation showed less infiltrating tumor cells and more lymphocytic infiltrations in the sLAK and EsLAK groups compared with the control group. These results suggest that induction of LAK cells by administration of SPG to lymphocytes treated by in vivo sensitization with tumor antigen increases the efficacy of adoptive immunotherapy.