Cure of murine Ehrlich ascites tumors with chronic oral indomethacin therapy combined with intraperitoneal administration of LAK cells and IL-2.
We have shown that prostaglandin E2-(PGE2) mediated inactivation of all killer lineage cells is a common event in the tumor-bearing 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 tumor-infiltrating 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 less than IL-2 + LAK cells less than CIT + IL-2 less than 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.
Lala
P K
PK
Department of Anatomy, University of Western Ontario, London, Canada.
Parhar
R S
RS
Singh
P
P
Lala
P K
PK
D000818:Animals; D001803:Blood Transfusion; D002286:Carcinoma, Ehrlich Tumor / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D002460:Cell Line; D003131:Combined Modality Therapy; D007213:Indomethacin / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008808:Mice, Inbred CBA; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control
D007376:Interleukin-2; D007213:Indomethacin