Regression and prevention of autochthonous tumors induced by 3-methylcholanthrene after injection of a T-cell receptor α/β positive and CD4/CD8 double negative T-cells

Abstract

Both the therapeutic and preventative effects of a murine T-cell line, tMK-2, with T-cell receptor (TCR) α/β positive and CD4 −/8 − double negative (DN) phenotype against autochthonously tumors induced by subcutaneous (s.c.) injection of 3-methylcholanthrene (MC) were examined. Complete regression of the tumor was observed when administration of tMK-2 cells was begun on tumors 5 mm in diameter. The tumor mass in five out of five mice was reduced in size after the administration of tMK-2 cells regardless of the routes of administration: s.c. injection of tMK-2 cells (5×10 7 cells) once a week around tumors, intraperitoneal (i.p.) injection (5×10 7 cells), or intravenous (i.v.) injection (1×10 7 cells). The tumors regressed to the status of a scar within 1 month of initial injection, and this status was maintained throughout the remainder of the 3 months period of tMK-2 cell injection. One month after discontinuation of tMK-2 cell administration, the diameter of the tumors had not increased regardless of the route of injection. The control groups consisted of either untreated mice, mice with i.v. injection of 1 μg of recombinant murine interleukin (IL)-12 once a week, or mice with s.c. injection of autologous splenocytes (5×10 7) from BALB/c mice once a week. Continuous growth of tumors was observed in each group and all control mice died due to bleeding ulcerations of the tumors. Tumor development was effectively prevented when tMK-2 cells were administrated 1 week after the s.c. injection of MC. In the groups receiving s.c., i.p., and i.v. injection of tMK-2 cells, no MC-induced tumors developed, whereas four out of five of the control mice developed autochthonous tumors. The tMK-2 cells also exerted in vitro NK-like cytotoxic activity, and their killing activity was strongly increased in the presence of both IL-2 and IL-12. These results suggest that the injected T-cells with TCR α/β positive and CD4 −/8 − DN phenotype and NK-like activity are important in the therapy as well as the prevention of tumor development.