We have used a murine
renal adenocarcinoma of spontaneous origin (Renca) inplanted in the peritoneal cavity to study the therapeutic potential of
biological response modifiers (BRMs) used alone or in conjunction with
chemotherapy. This
tumor model is therapeutically challenging since following intraperitoneal (i.p.) injection, the
tumor grows progressively with hemorrhagic
ascites, abdominal
metastases to lymph nodes, liver, spleen, most serous membranes, and, in some animals,
metastases to extra-abdominal sites (lungs). In the absence of
therapy, death invariably occurs within 36 +/- 2 days. The
tumor is efficiently lysed in 4 hours by peritoneal cells isolated from mice treated with BRMs. Both
MVE-2 and rIL-2 significantly increased the survival time of
tumor-bearing mice, but only treatment with
MVE-2 led to definite cures of i.p. Renca. A single i.p. injection of
MVE-2 cured 20% of the
tumor-bearing mice, while repeated i.p. administration of this
drug at 12 day intervals cured 70% of i.p. Renca-bearing mice. Combined
therapy with
doxorubicin hydrochloride and a single dose of
MVE-2 cured 90% of
tumor-bearing animals. The superior therapeutic efficiency of
MVE-2 compared to that of the rIL-2 may be due to its ability, after i.p. inoculation, to generate and maintain high levels of cytotoxic effector cell activity for an elevated period of time within the peritoneal cell population. Additionally,
MVE-2 augments effector cell activity in the liver, lungs, spleen, and blood and may therefore more efficiently interfere with
metastasis formation in those compartments. The additive effects of
MVE-2 and the chemotherapeutic agent suggest that more effective
therapy may be achieved by the combination of
immunotherapy with BRMs with chemotherapeutic drugs.