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.