EX vivo effector cell activation for target cell killing
AssigneeScripps Clinic and Research Foundation
InventorsCyril J. Honsik, Ralph A. Reisfeld
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Abstract
A method and composition for killing target cells is disclosed. The method utilizes ex vivo IL-2 activation of leucocyte effector cells and arming the activated leucocyte effectors with monoclonal antibodies whose Fc portions bind to the IL-2-activated effectors and whose paratopic portions immunoreact with an epitope expressed on the surfaces of the target cells. The composition contains a cytolytic amount of the armed, IL-2-activated effector cells dispersed in an aqueous physiologically tolerable diluent medium.
Claims20
A method of specifically killing of target cells consisting essentially of the steps of:
- (a) activating a culture of leucocytes containing IgG1, IgG2a, IgG2b or IgG3 antibody Fc receptors ex vivo with an amount of interleukin-2 sufficient to enhance the natural killer activity of said cells to form IL-2-activated effector cells;
- (b) separating said effector cells from toxic amounts of interleukin-2;
- (c) binding the Fc receptors of said IL-2-activated effector cells with Fc-containing monoclonal antibodies of class IgG1, IgG2a, IgG2b or IgG3 whose paratopic portions immunoreact with an antigen expressed on the surface of target cells to form armed, IL-2-activated effector cells;
- (d) contacting target cells with a cytotoxic amount of said armed, IL-2-activated effector cells in the absence of exogenous IL-2;
- and
- (e) maintaining said contact for a time period sufficient for said armed, IL-2-activated effector cells to kill said target cells.
A method of enhancing ADCC of tumor cells consisting essentially of the steps of:
- (a) activating a culture of peripheral blood mononuclear cells containing IgG1, IgG2a, IgG2b or IgG3 antibody Fc receptors ex vivo with an amount of interleukin-2 sufficient to enhance the natural killer activity of said cells to form IL-2-activated effector cells;
- (b) separating said IL-2-activated effector cells from toxic amounts of interleukin-2;
- (c) binding the Fc receptors of said IL-2-activated effector cells with Fc-containing monoclonal antibodies of class IgG1, IgG2a, IgG2b or IgG3 whose paratopic portions immunoreact with disialogangliosides GD2 or GD3 to form armed, IL-2-activated effector cells;
- (d) contacting a cytotoxic amount of said armed, IL-2-activated effector cells with tumor cells that express disialoganglioside selected from the group consisting cf GD2 and GD3 in the absence of exogenous IL-2;
- and
- (e) maintaining said contact for a time period sufficient for said armed, IL-2-activated effector cells to lyse said tumor cells.
A target cell killing composition consisting essentially of an aqueous physiologically tolerable diluent medium free of exogenous IL-2, containing dispersed therein an amount of armed, IL-2-activated effector cells from a leucocyte population effective to kill target cells, said IL-2-activated effector cells being armed with monoclonal antibodies of class IgGl1 IgG2a, IgG2b or IgG3 bound to the Fc receptors of said cells, the paratopic portions of said monoclonal antibodies immunoreacting with an antigen expressed on the surfaces of said target cells.
Dependencies are inferred from the claim text.