THE INHIBITORY EFFECT OF PREOPERATIVE IMMUNOCHEMOTHERAPY ON THE LYMPH-NODE METASTASIS OF MURINE MM48 TUMOR

A murine tumor model showing metastases to lymph nodes (LN) was establ ished by intradermally implanting highly metastatic MM48 tumor cells ( 2 X 10(6)) in C3H/HeN mice. We were searching for the most effective i mmunochemotherapeutic modality to treat this metastatic tumor. The com bination therapy with chemotherapeutics, granulocyte colony-stimulatin g factor (G-CSF) and OK-432 on Days 8-11 was found to be remarkably ef fective, making the solid tumor disappear in more than half of the tre ated mice, though all of them eventually died of LN metastasis, as all the control mice did. Then an attempt was made to cure the mice from such fatal metastatic tumors with combined immunochemotherapy prior to surgical resection on Day 14. The combination therapy with chemothera peutics, G-CSF and OK-432 more strongly inhibited the metastases then, and more than 85% of the mice survived. When the survivors were recha llenged with MM48 tumor cells, all of them rejected and survived witho ut recurrences and metastases, indicating the acquirement of specific immunity. It is expected that this preoperative immunochemotherapy may be clinically useful for the treatment of malignant neoplasms.