Treatment of adenocarcinoma in the peritoneum of mice: chemoimmunotherapy with IL-2-stimulated cytotoxic lymphocytes as a model for treatment of minimal residual disease.

We have used a transplantable murine adenocarcinoma of renal origin (Renca) introduced to the abdomen by i.p. injection of a tumor cell suspension, to study the therapeutic potential of adoptive immunotherapy and/or biological response modifiers (BRMs). This tumor model is therapeutically challenging since the tumor grows progressively resulting in extensive peritoneal carcinomatosis, with hemorrhagic ascites, metastases to abdominal lymph nodes, liver, most serous membranes, spleen, and in some animals, pulmonary metastases. Without therapy, death occurs invariably in 36 +/- 3 days. In vitro, the tumor is lysed by lymphocytes obtained from the peritoneal cavity of mice treated with human recombinant interleukin-2 (rIL-2) and by cytotoxic lymphocytes stimulated by in vitro culture with human rIL-2. Treatment of i.p. Renca with a single i.p. injection of the chemotherapeutic agent doxorubicin hydrochloride (DOX), or adoptive transfer of in vitro stimulated cytotoxic lymphocytes together with rIL-2 cured 50% and 20% of the tumor-bearing mice, respectively. In contrast, combined therapy with DOX and adoptive transfer of in vitro stimulated cytotoxic lymphocytes and rIL-2 cured the majority (90%) of tumor-bearing mice. These results suggest that administration of immunotherapy with in vitro activated cytotoxic cells together with human rIL-2 substantially enhances the effectiveness of chemotherapy.