COMBINATION CHEMOIMMUNOTHERAPY OF MURINE SOLID TUMOR WITH OK-432, G-CSF,, IL-2, AND CHEMOTHERAPEUTICS

An experimental tumor model was previously established in which BALB/c mice could survive the otherwise fatal intraperitoneal (i.p.) inocula tion of BAMC-1 fibrosarcoma cells if the mice were treated with five s equential i.p. injections of OK-432 (a potent BRM) starting Z days aft er tumor inoculation. In the present study, although a single i.p. inj ection of OK-432 alone on day 2 was not enough to cure the tumor-beari ng mice, a combination therapy, an injection of OK-432 (5 mg/kg) on da y 2 followed by injection of G-CSF (50 mu g/kg) on day 3, could eradic ate the tumor cells in more than 80% of the mice. In contrast to this ascites tumor model, solid tumors induced by intradermal transplantati on of BAMC-1 tumor cells were resistant to the combined treatments wit h OK-432 and G-CSF, dying within 60 days. However, when these mice rec eived a combined chemoimmunotherapy with cisplatin, OK-432, G-CSF and IL-2, starting on day 4, the tumors had regressed, and were completely eradicated. When the same treatment was started as late as day 8, no significant therapeutic effect was observed. Even at this advanced sta ge, however, it was found that a similar chemo-immunotherapy protocol using CAP-D (cyclophosphamide, epirubicin and DWA2114R) in lieu of cis platin was extremely effective, achieving the eradication of rumors in more than 70% of the mice. These results indicated that the combinati on therapy with OK-432, G-CSF, IL-2, and chemotherapeutics could achie ve a potent anti-tumor effect against the solid tumor, even at the adv anced stage. Subsequent experiments using athymic nude mice transplant ed with the tumor cells revealed that the same combination therapy sho wed weak tumor-regressing effects without achieving a complete cure. T hese results suggest that T-cells are key effecters in this type of ch emo-immunotherapy of malignant tumors.