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Adjuvant Immunotherapy of Established Murine Renal Cancer by Interleukin 2-stimulated Cytotoxic Lymphocytes¹

Biological Therapeutics Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, NIH, Frederick Cancer Research Facility, Frederick, Maryland [R. R. S., R. H. W.], and the Department of Urology, Johannes Gutenberg University Medical School, Mainz, West Germany [R. R. S.]

We have used a transplantable experimental murine renal carcinoma (Renca) to evaluate the adjuvant immunotherapeutic potential of cytotoxic lymphocytes stimulated by in vitro incubation for 24 h with human recombinant interleukin 2 (rIL-2). The Renca tumor model is therapeutically challenging since, following intrarenal implant, it grows progressively with local invasion and development of spontaneous metastases in abdominal lymph nodes, lungs, and liver. Therefore, successful treatment requires control of both primary tumor, local and regional invasive growth, and systemic metastases. Our studies have shown that rIL-2-stimulated cytotoxic lymphocytes efficiently lyse Renca in vitro. Further, both doxorubicin hydrochloride and an active metabolite of cyclophosphamide also inhibited the growth of Renca in vitro. In vivo administration of doxorubicin hydrochloride, cyclophosphamide or rIL-2-stimulated cytotoxic lymphocytes and rIL-2 to mice bearing established Renca tumors (7-day disease) resulted in a significant (P < 0.01) increase in short-term survivors (at 45 days), but only 17% cures. However, combination chemoimmunotherapy consisting of doxorubicin hydrochloride and rIL-2-stimulated cytotoxic lymphocytes plus rIL-2 results in the cure of 67% of mice bearing established Renca. These results demonstrate that chemotherapy and immunotherapy with adoptively transferred cytotoxic lymphocytes can function synergistically in the treatment of established murine renal carcinoma.

¹ This project has been funded at least in part with Federal funds from the Department of Health and Human Services, under Contract NO1-CO-23910 with Program Resources, Inc.

² Supported by Grant SA 364/1-1 from Deutsche Forschungsgemeinschaft, West Germany.

Received 6/18/85. Revised 10/28/85. Revised 2/17/86. Accepted 3/31/86.

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