Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.
Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of peripheral blood lymphocytes (PBL) which can mediate augmented tumor cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma and renal carcinoma have shown measurable tumor responses in 10-20% of human patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant treatment for canine tumors. In order to evaluate the possibility to extend the use of IL-2 in vivo in the dog, we examined the ability of a clinically relevant (low) dose of human recombinant IL-2 (100 units/ml) to enhance the tumoricidal properties of canine PBL in vitro. This was particularly important considering the need to establish the effects on canine PBL by IL-2 at a dose that is potentially achievable in vivo with acceptable side effects. Our data show, for the first time, the ability to separate canine natural killer (NK) cell activity from lymphokine-activated killer (LAK) cell activity (induced with a low IL-2 dose) mediated by canine PBL against two canine cell lines (CTAC and CML-10) used as targets in 4 vs. 16 hour killing assays. LAK cells generated by stimulation of canine PBL with 100 units/ml of IL-2 for 72 hours, could kill CTAC or CML-10 targets up to 11 or 18 times more efficiently, respectively, than fresh PBL in a 4 hour assay. However, the killing of efficiency of the LAK cells was only 2- to 3-fold greater than that of the fresh PBL in a 16 hour assay. This apparent reduction in the killing efficiency of the LAK cells was mostly due to increased spontaneous NK activity by the fresh PBL after 16 hours in culture; both the LAK cells and the fresh PBL (NK cells) mediated a greater overall cytotoxicity after 16 hours than they did in the 4 hour assays. These results indicate that a low dose of human recombinant IL-2 can augment tumor killing by canine PBL in vitro, and suggest that it may be feasible to examine the potential use of IL-2 as an immunotherapeutic agent in tumor-bearing dogs.
Helfand
S C
SC
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Soergel
S A
SA
Modiano
J F
JF
Hank
J A
JA
Sondel
P M
PM
D000230:Adenocarcinoma / Q000473:pathology / Q000662:veterinary; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004283:Dog Diseases / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000662:veterinary*; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000662:veterinary; D009369:Neoplasms / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D013964:Thyroid Neoplasms / Q000473:pathology / Q000662:veterinary; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins