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 i nvestigated in two experimental tumor models, 3MC-induced MHC class I+ sarc oma Mc12 and HPV16 E6/E7 oncogene-induced MHC class I- carcinoma MK16, tran splanted in syngeneic mice. Treatment of Mc12 and MK16 tumor-bearing mice w ith GM-CSF or CBM-4A alone produced moderate anti-tumor effects. However, w hen the tumor-bearing mice were first treated i.p. with a single dose of CB M-4A (150 mg/kg) and three days later peritumorally with five daily doses o f GM-CSF (100 ng/day), substantially stronger tumor-inhibitory effects were observed. The results indicate that in both, MHC class I+ and MHC class P tumors, the combined chemoimmunotherapy can inhibit tumor progression more effectively than GM-CSF therapy or chemotherapy alone, and they suggest tha t GM-CSF should be considered as adjuvant to chemotherapy in clinical trial s with HPV 16-associated neoplasms.