IP Library Granted Patent US 8,153,120
Granted Patent B2
US 8,153,120 · App. 12/077,823 · Granted Apr 10, 2012

Methods for inducing a natural killer (NK) cell-mediated immune response and for increasing NK cell activity

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Quick Facts
Patent No.
US 8,153,120
App. No.
12/077,823
Granted
Apr 10, 2012
Kind
B2
Abstract

The present invention relates to the discovery of novel 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. The method comprises the steps of isolating peripheral blood mononuclear cells (PBMCs) from the subject, exposing the PBMCs in vitro to protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen, under conditions effective to activate the PBMCs, and administering the activated PBMCs to the subject. The invention also relates to a method of detecting in a subject a cytotoxic NK cell-meditated immune response or NK cell activity in vitro by CD336 expression and/or lysis of the K562 tumor line. The invention further relates to a method for determining whether a subject has had a therapeutically effective response to a protein conjugate by assessing the NK activity of activated PBMCs from the subject.

Claims (13)

1. In a method for treating cancer in a mammalian subject by

(a) isolating PBMCs from a subject;

(b) exposing the 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 the PBMCs;

(c) administering the activated PBMCs to the subject;

(d) repeating step (a) and (b) at least 10 days after previous step (c) has occurred, an improvement for determining whether the subject has shown a positive therapeutic response to the treatment and therefore whether the subject is a candidate for additional treatment with activated PBMCs, comprising

(i) assessing an NK activity of the activated PBMCs from the second isolation;

(ii) comparing the assessed NK level from step (i) with an NK level assessed prior to first administering the activated PBMCs to the subject; and

(iii) if the level of NK activity assessed in step (i) has increased significantly over the level of NK activity assessed prior to the first administration, classifying the subject as having shown a positive therapeutic response to the treatment and therefore being a good candidate for additional treatment by activated PBMC administration.

2. The method of claim 1 , wherein said steps (a) through (c) are performed a total of two times and wherein 14 days have elapsed since the previous step (c) has occurred.

3. The method of claim 1 , wherein said step (i) is performed in vitro by CD336 surface expression.

4. The method of claim 1 , wherein said step (i) is performed in vitro by lysis of the K562 tumor line.

5. The method of claim 1 , wherein said mammalian subject is a human.

6. The method of claim 1 , wherein said protein conjugate is produced in a baculovirus expression system.

Assignments (7)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE ADDRESS PREVIOUSLY RECORDED AT REEL: 042389 FRAME: 505. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF NAME. Recorded Feb 14, 2018
From: DENDREON PHARMACEUTICALS, INC.
To: DENDREON PHARMACEUTICALS LLC
Reel/Frame 046088/0882 →
RELEASE OF SECURITY INTEREST Recorded Jul 5, 2017
From: BARCLAYS BANK PLC
To: DENDREON PHARMACEUTICALS LLC
Reel/Frame 043089/0288 →
CHANGE OF NAME Recorded May 3, 2017
From: DENDREON PHARMACEUTICALS, INC.
To: DENDREON PHARMACEUTICALS LLC
Reel/Frame 042389/0505 →
SECURITY AGREEMENT Recorded Jul 27, 2015
From: DENDREON PHARMACEUTICALS, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 036190/0503 →
CHANGE OF NAME Recorded Jul 20, 2015
From: DRONE ACQUISITION SUB INC.
To: DENDREON PHARMACEUTICALS, INC.
Reel/Frame 036136/0181 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 16, 2015
From: DENDREON CORPORATION, AND ITS WHOLLY OWNED SUBSIDIARIES, DENDREON HOLDINGS, LLC, DENDREON DISTRIBUTION, LLC, AND DENDREON MANUFACTORING, LLC
To: DRONE ACQUISITION SUB INC.
Reel/Frame 036126/0259 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 6, 2009
From: SHEIKH, NADEEM; JONES, LORI
To: DENDREON CORPORATION
Reel/Frame 022357/0017 →