In vivo generation of lymphokine activated killer cell activity by ABPP and interleukin-2 and their antitumor effects against immunogenic and nonimmunogenic tumors in murine tumor models.
The capacity of the interferon inducer ABPP and recombinant interleukin-2 (IL-2) to generate lymphokine activated killer (LAK) cell activity in vivo was examined and compared to the cytolysis of fresh tumor cells by in vitro generated LAK cells. Various tumors differing in histology and immunogenicity were used in vitro and in vivo experiments. The i.p. administration of ABPP or IL-2 generated much higher levels of LAK cell activity in the peritoneal exudate than in the spleen. Administration of 2 injections of ABPP was as effective as a 3-day course of moderate doses of IL-2. Generation of LAK cell activity by IL-2 was dose dependent. ABPP had significant antitumor activity in vivo in both the i.p. tumor model and the pulmonary metastasis model when administered early (24-48 h after tumor inoculation), but was ineffective against established (day 3) tumor or advanced grossly visible i.p. (day 8) tumor. Treatment of established tumor with IL-2 and LAK cells was not more effective when ABPP was given concurrently. In contrast when ABPP preceded IL-2 and LAK treatment an additional antitumor effect was seen. Immunogenic tumors were more sensitive to treatment with ABPP than nonimmunogenic tumors. Only a marginal difference in lysability in vitro existed. The antitumor effects of ABPP in vivo may therefore be mediated by mechanisms other than cytolysis by activated killer cells alone. These data taken together suggest that ABPP and IL-2 induce discernable levels of LAK cell activity, but do not synergize when combined.
Eggermont
A M
AM
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Sugarbaker
P H
PH
Marquet
R L
RL
Jeekel
J
J
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007376:Interleukin-2; D003596:Cytosine; C033560:bropirimine