Sequential chemoimmunotherapy with cisplatin, interferon-beta and interleukin-2 inhibits the growth of B16-F1 melanoma in syngeneic mice.
Sequential combinations of chemotherapy with biological response modifiers has recently been evaluated as systemic treatment for patients with advanced melanoma. The response rates of the chemoimmunotherapy were reported to be higher than conventional treatment using chemotherapy or biological agents alone. To investigate the effectiveness of such chemoimmunotherapy, we evaluated the antitumour effect of sequential chemoimmunotherapy in vivo using a B16 mouse melanoma system. In this sequential regimen, administration of cisplatin (CDDP) was followed by interferon-beta (IFNbeta) and interleukin-2 (IL-2). This combination therapy synergistically inhibited the growth of B16-F1 melanoma and prolonged the survival of mice bearing B16-F1. In contrast, this therapy did not show any antitumour effect on B16-F10 melanoma. The exact mechanism of the antitumour effect is not clear, but the following results were noted: no synergistic effect of this therapy was detected in nude mice, neutralizing anti-IFNgamma antibody significantly blocked the antitumour effect of this therapy, and the number of apoptotic melanoma cells was significantly increased in melanoma tissues removed from mice treated with this therapy. These results demonstrated the potent immunological antitumour effect of this sequential chemoimmunotherapy.
Kubo
H
H
Department of Dermatology, Shinshu University School of Medicine, Asahi Matsumoto, Japan.
Matsumoto
K
K
Funahashi
M
M
Takagi
H
H
Kitajima
Y
Y
Taniguchi
S
S
Saida
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D007167:Immunotherapy; D016899:Interferon-beta / Q000008:administration & dosage; D007376:Interleukin-2 / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D016899:Interferon-beta; D002945:Cisplatin