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).
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.
Department of Oncology, Radiumhemmet, Immunologic Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
G
G
Masucci
P
P
Ragnhammar
P
P
Wersäll
H
H
Mellstedt
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor