Chemoimmunotherapy of cancer: potentiated effectiveness of granulocyte-macrophage colony-stimulating factor and ifosfamide derivative CBM-4A.
The effectiveness of combined chemoimmunotherapy with ifosfamide derivative CBM-4A and granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in two experimental tumor models, 3MC-induced MHC class I+ sarcoma Mc12 and HPV16 E6/E7 oncogene-induced MHC class I- carcinoma MK16, transplanted in syngeneic mice. Treatment of Mc12 and MK16 tumor-bearing mice with GM-CSF or CBM-4A alone produced moderate anti-tumor effects. However, when the tumor-bearing mice were first treated i.p. with a single dose of CBM-4A (150 mg/kg) and three days later peritumorally with five daily doses of GM-CSF (100 ng/day), substantially stronger tumor-inhibitory effects were observed. The results indicate that in both, MHC class I+ and MHC class I- tumors, the combined chemoimmunotherapy can inhibit tumor progression more effectively than GM-CSF therapy or chemotherapy alone, and they suggest that GM-CSF should be considered as adjuvant to chemotherapy in clinical trials with HPV 16-associated neoplasms.
Indrová
M
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Bubeník
J
J
Símová
J
J
Bieblová
J
J
Jandlová
T
T
Smahel
M
M
Vonka
V
V
Glazman-Kusnierczyk
H
H
Pajtasz-Piasecka
E
E
Radzikowski
C
C
Mikysková
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D012509:Sarcoma / Q000188:drug therapy* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C097983:chlorobromofosfamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide