Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.

TitleInduction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.
Publication TypeJournal Article
Year of Publication1994
AuthorsHelfand SC, Soergel SA, Modiano JF, Hank JA, Sondel PM
JournalCancer biotherapy
Date Published1994 Fall
KeywordsAdenocarcinoma, Animals, Cells, Cultured, Cytotoxicity, Immunologic, Dog Diseases, Dogs, Feasibility Studies, Female, Humans, Immunotherapy, Adoptive, Interleukin-2, Killer Cells, Lymphokine-Activated, Male, Melanoma, Neoplasms, Recombinant Proteins, Species Specificity, Thyroid Neoplasms, Tumor Cells, Cultured

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.

Alternate JournalCancer Biother.