Adoptive immunotherapy with lymphokine-activated killer (LAK) cells induced by Interleukin 2 (IL2) has provided a new and promising strategy for the treatment of cancer patients. The clinical observation of variable degrees of cytopenia(s) in patients with solid tumors treated with LAK cells suggests that IL2-activated effector cells may play a role on the normal progenitor cell compartment. We therefore carried out in vitro studies designed to assess the influence of LAK cells on normal hemopoiesis. LAK cells from different individuals were cultured with enriched normal peripheral blood and bone marrow colony-forming cells at effector: target ratios ranging between 1:1 and 10:1. Both LAK effectors generated from peripheral blood mononuclear non-adherent cells (PBL-LAK) and from sheep erythrocyte rosette-forming cells (RFC-LAK) suppressed in a reproducible manner the growth of CFU-GM and CFU-E from both peripheral blood and bone marrow. This inhibitory effect is dose-dependent, appears to be smaller with LAK cells generated from RFC rather than from unfractionated PBL and is less evident on the early erythroid compartment. In general, the effect is more pronounced when LAK cells are pre-incubated for 18 hours with the target cell populations prior to seeding. Both autologous and allogeneic PBL-LAK inhibit colony formation. The mechanism of killing implicates a release of soluble factor(s) after close cell-to-cell interaction, as only cell-free supernatants produced after pre-incubation of PBL-LAK cells with hemopoietic progenitors give rise to inhibitory effects. The evidence that during this incubation time high levels of Tumor Necrosis Factor-alpha (TNF) are released and that the use of an anti-TNF antibody completely abolishes the inhibitory effect suggests that TNF plays a part in the LAK cell-induced inhibitory activity.
Lymphokine Activated Killer (LAK) Cells Inhibit the in vitro Growth of Myeloid and Erythroid Progenitor Cells Via the Release of Tumor Necrosis Factor-Alpha
BELLONE, Graziella;FIERRO, Maria Teresa;PEGORARO, Luigi;
1990-01-01
Abstract
Adoptive immunotherapy with lymphokine-activated killer (LAK) cells induced by Interleukin 2 (IL2) has provided a new and promising strategy for the treatment of cancer patients. The clinical observation of variable degrees of cytopenia(s) in patients with solid tumors treated with LAK cells suggests that IL2-activated effector cells may play a role on the normal progenitor cell compartment. We therefore carried out in vitro studies designed to assess the influence of LAK cells on normal hemopoiesis. LAK cells from different individuals were cultured with enriched normal peripheral blood and bone marrow colony-forming cells at effector: target ratios ranging between 1:1 and 10:1. Both LAK effectors generated from peripheral blood mononuclear non-adherent cells (PBL-LAK) and from sheep erythrocyte rosette-forming cells (RFC-LAK) suppressed in a reproducible manner the growth of CFU-GM and CFU-E from both peripheral blood and bone marrow. This inhibitory effect is dose-dependent, appears to be smaller with LAK cells generated from RFC rather than from unfractionated PBL and is less evident on the early erythroid compartment. In general, the effect is more pronounced when LAK cells are pre-incubated for 18 hours with the target cell populations prior to seeding. Both autologous and allogeneic PBL-LAK inhibit colony formation. The mechanism of killing implicates a release of soluble factor(s) after close cell-to-cell interaction, as only cell-free supernatants produced after pre-incubation of PBL-LAK cells with hemopoietic progenitors give rise to inhibitory effects. The evidence that during this incubation time high levels of Tumor Necrosis Factor-alpha (TNF) are released and that the use of an anti-TNF antibody completely abolishes the inhibitory effect suggests that TNF plays a part in the LAK cell-induced inhibitory activity.
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