Curative treatments of murine Colon26 solid tumors by immunochemotherapy with G-CSF and OK-432.
In order to study the clinical usefulness of biological response modifiers (BRMs) in eliminating malignant solid tumors, we have investigated the effect of various combination therapies on the murine Colon26 solid tumor model. When the tumor-bearing mice were treated with chemotherapeutics, G-CSF and OK-432 (streptococcal preparation), the tumors completely disappeared from all of the treated mice. When these survivors were rechallenged with Colon26 tumor cells on Day 120, all of them survived without showing any sign of recurrence or metastases. The results indicate that mice with malignant solid tumors, which can not be cured using chemotherapeutics alone, may be completely healed with a combination immuno-chemotherapy. During the course of this combination therapy, study, it was found that there was a clear positive correlation between immunosuppressive acidic protein (IAP) levels and tumor sizes. Suppressor macrophages (sM phi) which produce IAP were found to be decreased in bone marrow and spleen of treated mice. This suggests that the combination therapy may make the mice recover from a suppressed immune state caused by sM phi. In conclusion, the combination therapy with chemotherapeutics and BRMs could cure the solid tumor-bearing mice very effectively through not only synergistic direct tumor cell destruction but also indirect immunomodulation of the host.
Kudo
C
C
Central Research Laboratories, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Saito
M
M
Yoshida
T
T
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage; D008264:Macrophages / Q000145:classification / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000097:blood; D010844:Picibanil / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D007155:Immunologic Factors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C030193:immunosuppressive acidic protein; C058816:DWA 2114; D016179:Granulocyte Colony-Stimulating Factor; D010844:Picibanil; D015251:Epirubicin; D016685:Mitomycin; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin