Methods for inducing a natural killer (nk) cell-mediated immune response and for increasing nk cell activity
AssigneeDendreon Corporation
InventorsNadeem Sheikh, Lori Jones
Life of this patent
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Abstract
This disclosure relates to methods of inducing a natural killer (NK) cell-mediated immune response and increasing NK activity in a mammal for the treatment of tumors and virus infections, comprising isolating peripheral blood mononuclear cells (PBMCs) from a subject, exposing them in vitro to a protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen to activate the PBMCs, and administering the activated PBMCs to the subject. The method also relates to assessing NK cell activity of activated PBMCs to determine whether the subject has had a therapeutically effective response to the protein conjugate.
Claims22
A method for detecting a cytotoxic NK cell-mediated immune response in a subject, comprising:
- (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject;
- (b) exposing said PBMCs in vitro to a protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen selected from the group consisting of a tumor associated antigen (TAA) and an oncogene product, under conditions effective to activate said PBMCs;
- (c) assessing the level of an NK cell response in the activated PBMCs;
- (d) administering said activated PBMCs to the subject;
- (e) repeating steps (a) and (b) at least 10 days after the previous step (d) has occurred, resulting in a second isolation of PMBCs;
- and
- (e) assessing the level of an NK cell response in the activated PBMCs from the second isolation, wherein said activated PBMCs are effective in activating NK cells to produce a cytotoxic cellular response at a level higher than that produced by the PBMCs which have not been activated by the protein conjugate.
A method for determining whether a subject has had a therapeutically effective response to a protein conjugate, comprising,
- (a) isolating PBMCs from the subject;
- (b) exposing said PBMCs in vitro to a protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen selected from the group consisting of a tumor associated antigen (TAA) and an oncogene product, under conditions effective to activate said PBMCs;
- (c) administering said activated PBMCs to the subject;
- (d) repeating steps (a) and (b) at least 10 days after step (c) has occurred;
- and
- (e) determining a change in NK cell activity of the activated PBMCs.
Dependencies are inferred from the claim text.