In vivo tumouricidal 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 the host-tumour immune mechanism was assessed using 9,10-dimethyl-1,2-benzanthracene induced rat malignant fibrous histiocytoma (MFH). The antitumour effect of LADM was analyzed using a double grafted tumour system in which F344 rats first received simultaneous s.c. inoculations of MFH cells in both right and left flanks and were then injected with 0.2 mg 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 infiltration of CD8+ or CD4+ cells at the tumour periphery was histologically revealed. This inhibition was not observed in F344 nu/nu athymic rats. Winn neutralizing assay with T cell-rich splenic lymphocytes from each drug-treated MFH-bearing rat showed that complete regression of 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 FACS sorting splenic lymphocytes. These results strongly suggest that intratumoural administration of LADM caused the systemic augmentation of the MFH-bearing host immune mechanism, and that the augmented response after LADM treatment was induced by the cytotoxic CD8+ lymphocytes dependent on the CD4+ lymphocytes.
Yakushiji
T
T
Department of Orthopaedic Surgery, Kumamoto University School of Medicine, Japan.
Yonemura
K
K
Nishida
K
K
Takagi
K
K
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D004337:Drug Carriers; D018219:Histiocytoma, Benign Fibrous / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016219:Immunotherapy, Adoptive; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin