Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Enhanced human lymphokine-activated killer cell function after brief exposure to granulocyte-macrophage-colony stimulating factor.
Cancer. 1995 Oct 1;76(7):1253-60. Unique Identifier : AIDSLINE MED/96223172 Baxevanis CN; Dedoussis GV; Papadopoulos NG; Missitzis I; Beroukas C; Stathopoulos GP; Papamichail M; Department of Immunology, Hellenic Anticancer Institute, Athens,; Greece.
Abstract:
BACKGROUND. Lymphokine-activated killer (LAK) cell function can be generated in peripheral blood mononuclear cells (PBMC) after brief exposure of high dose interleukin-2 (IL-2) over the course of 1 or 2 days' culture in plain culture medium (IL-2-pulsed PBMC). The aim of the present study was to investigate the ability of granulocyte-macrophage-colony stimulating factor (GM-CSF) to augment LAK induction in low dose IL-2-pulsed PBMC derived from patients with cancer undergoing immunotherapy with IL-2. METHODS. Peripheral blood mononuclear cells were collected from patients with cancer receiving a 5-day cycle of local (intraperitoneal or intrapleural) infusions with IL-2. The cells were incubated with IL-2 in the presence or absence of GM-CSF for 1 hour and then tested as effectors against allogeneic tumor cells and LAK-sensitive cell lines. RESULTS. Granulocyte-macrophage-colony stimulating factor at doses between 10 and 100 ng/ml was synergized with low dose IL-2 (100 IU/ml) in the generation of LAK activity in PBMC. Lymphokine-activated killer cell-mediated cytotoxicity derived from PBMC cultures incubated with IL-2 and GM-CSF was significantly higher (up to three-fold) compared with that generated with IL-2 alone. The GM-CSF-induced enhanced LAK activity was maintained when tested at day 5. GM-CSF increased the percentages of IL-2 receptor (R) positive (+) and CD8+ cells in the IL-2-pulsed PBMC. In contrast to CD56+ cells, highly purified CD8+ cells isolated from PBMC pulsed with IL-2 and GM-CSF responded with increased LAK activity, thus representing the cell-type that mediates the augmenting effect of GM-CSF. Major histocompatibility complex (MHC) molecules or the CD3 surface antigens were not involved in the GM-CSF-mediated enhancement of LAK induction because anti-MHC class I and class II monoclonal antibodies (MoAb) or MoAb against the CD3 molecules remained without any effect in this system. The GM-CSF-mediated LAK-enhancement was IL-2-dependent because MoAb against IL-2 receptor completely inhibited the generation of LAK activity. CONCLUSIONS. The use of GM-CSF for the enhancement of IL-2-induced LAK activity in 1 hour cultures may improve clinical results in cancer immunotherapy. In addition, implementation of this procedure could eliminate the high cost of cell culture which usually accompanies IL-2/LAK cell therapy as well as eliminate the known toxic side effects associated with this kind of therapy.
Keywords: Adolescence Adult Aged Antigens, CD56/METABOLISM Cells, Cultured Child Child, Preschool Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/IMMUNOLOGY Female Granulocyte-Macrophage Colony-Stimulating Factor/*PHARMACOLOGY Human Immunotherapy, Adoptive/METHODS Interleukin-2/PHARMACOLOGY Killer Cells, Lymphokine-Activated/*IMMUNOLOGY Male Receptors, Interleukin-2/METABOLISM JOURNAL ARTICLE 960930
M9690923
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
