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

Cancer Biother. Fall 1994;9(3):237-44. doi: 10.1089/cbr.1994.9.237.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / veterinary
  • Animals
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects
  • Dog Diseases / pathology
  • Dog Diseases / therapy*
  • Dogs
  • Feasibility Studies
  • Female
  • Humans
  • Immunotherapy, Adoptive / veterinary*
  • Interleukin-2 / pharmacology*
  • Killer Cells, Lymphokine-Activated / drug effects*
  • Killer Cells, Lymphokine-Activated / immunology
  • Male
  • Melanoma / pathology
  • Melanoma / veterinary
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neoplasms / veterinary*
  • Recombinant Proteins / pharmacology
  • Species Specificity
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / veterinary
  • Tumor Cells, Cultured

Substances

  • Interleukin-2
  • Recombinant Proteins