Granulocyte-monocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A)

Cancer Immunol Immunother. 1990;31(4):231-5. doi: 10.1007/BF01789174.

Abstract

Blood lymphocytes stimulated for 96 h with interleukin-2 (IL-2; 100 BRMP U/ml) (lymphokine-activated killer, LAK, cells) or granulocyte-monocyte colony-stimulating-factor (GM-CSF) (10 ng/ml) became cytotoxic for Daudi cells. IL-2 was significantly more effective than GM-CSF. Only IL-2-activated cells killed SW948 (a human colorectal carcinoma cell line) while GM-CSF-stimulated cell did not. GM-CSF and IL-2 acted synergistically in a dose-dependent fashion for induction of a highly effective cytotoxic cell population (IL-2/GM-CSF cells). Il-2/GM-CSF cells were statistically significantly more effective than LAK cells in lysing Daudi cells and SW948 (P less than 0.05). The enhancing effect was most pronounced during the first 48-96 h of activation. Incubation periods longer than 192 h did not contribute to augmented cytotoxicity. The combination of IL-2 and GM-CSF significantly increased the number of CD25+ cells compared to IL-2 and GM-CSF alone. Furthermore, IL-2/GM-CSF cells were significantly more effective in antibody-dependent cellular cytotoxicity assays (SW948 + mAb 17-1A) than LAK cells. The chimeric mAb 17-1A was significantly more effective in tumor cell lysis than the mouse mAb. Thus, combination of various biological therapeutics might be a way to enhance their antitumoral effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibody-Dependent Cell Cytotoxicity / physiology
  • Colony-Stimulating Factors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Growth Substances / pharmacology*
  • Humans
  • Interleukin-2 / pharmacology*
  • Killer Cells, Lymphokine-Activated / drug effects
  • Killer Cells, Lymphokine-Activated / physiology
  • Kinetics
  • Lymphocyte Activation / drug effects*
  • Mice
  • Receptors, Interleukin-2 / physiology
  • T-Lymphocytes, Cytotoxic / physiology*
  • T-Lymphocytes, Cytotoxic / ultrastructure

Substances

  • Antibodies, Monoclonal
  • Colony-Stimulating Factors
  • Growth Substances
  • Interleukin-2
  • Receptors, Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor