Cure of murine Ehrlich ascites tumors with chronic oral indomethacin therapy combined with intraperitoneal administration of LAK cells and IL-2

Abstract

We have shown that prostaglandin E 2-(PGE 2) mediated inactivation of all killer lineage cells is a common event in the tumorbearing host, so that chronic indomethacin therapy (CIT) combined with multiple rounds of IL-2 cures spontaneous and experimental metastases of a variety of murine tumors by activating killer cells in situ. Ehrlich ascites tumor (EAT) is fatal for any mouse strain even with a small i.p. inoculum. We compared the therapeutic efficacy of chronic indomethacin therapy (CIT), CIT + interleukin-2 (IL-2), IL-2 + lymphokine activated killer (LAK) cells and CIT + IL-2 + LAK cells on EAT grown in CBA mice. CIT alone retarded tumor growth and stimulated cytotoxic activity in splenocytes as well as tumorinfiltrating lymphocytes against YAC-1 lymphoma and EAT targets but resulted in no cure. The therapeutic efficacy in prolonging the median survival improved in the following order: CIT < IL-2 + LAK cells < CIT + IL-2 < CIT + IL-2 + LAK cells. The last regimen cured 90% of mice and resulted in a short-lasting immunity against a second tumor challenge in some of the animals. Thus, this triple combination therapy may hold promise for eradicating carcinomatous ascites in the human.