IN-VIVO TUMORICIDAL EFFECT OF T-LYMPHOCYTES ACTIVATED BY LIPOSOMES CONTAINING ADRIAMYCIN ON CHEMICALLY-INDUCED RAT MALIGNANT FIBROUS HISTIOCYTOMA

The augmentative effect of liposomes containing adriamycin (LADM) in t he host-tumour immune mechanism was assessed using 9,10-dimethyl-1,2-b enzanthracene induced rat malignant fibrous histiocytoma (MFH). The an titumour effect of LADM was analyzed using a double grafted tumour sys tem in which F344 rats first received simultaneous s.c. inoculations o f MFH cells in both right and left flanks and were then injected with 0.2mg of LADM into the right tumour on Day 10, 12, and 14. The growth of a remote, non-treated tumour was strongly inhibited and the infiltr ation of CD8(+) or. CD4(+) cells at the tumour periphery was histologi cally revealed. This inhibition was not observed in F344 nu/nu athymic rats. Winn neutralizing assay with T cell-rich splenic lymphocytes fr om each drug-treated MFH-bearing rat showed that complete regression o f the tumour at a low effector/target ratio occurred only in the LADM- treated group. Furthermore, the tumouricidal effects were demonstrated in coexistence with CD8(+) cells and CD4(+) cells by assay with FAGS sorting splenic lymphocytes. These results strongly suggest that intra tumoural administration of LADM caused the systemic augmentation of th e MFH-bearing host immune mechanism, and that the augmented response a fter LADM treatment was induced by the cytotoxic CD8(+) lymphocytes de pendent on the CD4(+) lymphocytes.