Compositions and methods to accelerate hematologic recovery
The present invention relates generally to methods for activating and expanding T cells, and more particularly, to methods for restoring hematologic function and/or accelerating hematologic recovery in patients by administering said T cells. Compositions of cells activated and expanded by the methods herein are further provided.
1 . A method for accelerating hematologic recovery in a patient exhibiting reduced hematologic function, comprising:
(i) contacting a population of cells from the patient wherein at least a portion thereof comprises T cells with a surface, wherein said surface has attached thereto a first agent that ligates a first cell surface moiety of a T cell, and the same or a second surface has attached thereto a second agent that ligates a second moiety of said T cell, wherein said ligation by the first and second agent induces proliferation of said T cell
(ii) administering to the patient the population of T cells of (i);
thereby accelerating hematologic recovery in the patient.
2 . The method of claim 1 wherein the first agent comprises an anti-CD3 antibody or an antigen binding fragment thereof and said second agent comprises a ligand which binds an accessory molecule on the surface of said T cells.
3 . The method of claim 2 wherein said accessory molecule is CD28.
4 . The method of claim 1 wherein the first agent comprises an anti-CD3 antibody or an antigen binding fragment thereof and said second agent comprises an anti-CD28 antibody or an antigen binding fragment thereof.
5 . The method of claim 1 wherein said first and second agents are attached to said surface or said second surface by covalent attachment.
6 . The method of claim 1 wherein said first and second agents are attached to said surface or said second surface by direct attachment.
7 . The method of claim 1 wherein said first and second agents are attached to said surface or said second surface by indirect attachment.
8 . The method of claim 1 wherein the patient is afflicted with a cancer.
9 . The method of claim 8 wherein the cancer is selected from the group consisting of multiple myeloma, prostate cancer, and chronic lymphocytic leukemia.
10 . The method of claim 1 wherein the hematologic recovery comprises one or more of an increase in neutrophil counts, an increase in platelet counts, an increase in hemoglobin levels, and an increase in NK cell counts.
11 . A method for accelerating neutrophil recovery in a patient, comprising:
(i) contacting a population of cells from the patient wherein at least a portion thereof comprises T cells with a surface, wherein said surface has attached thereto a first agent that ligates a first cell surface moiety of a T cell, and the same or a second surface has attached thereto a second agent that ligates a second moiety of said T cell, wherein said ligation by the first and second agent induces proliferation of said T cell
(ii) administering to the patient the population of T cells of (i);
thereby accelerating neutrophil cell recovery in the patient.
12 . The method of claim 11 wherein the first agent comprises an anti-CD3 antibody or an antigen binding fragment thereof and said second agent comprises a ligand which binds an accessory molecule on the surface of said T cells.
12 . The method of claim 11 wherein said accessory molecule is CD28.
14 . The method of claim 11 wherein the first agent comprises an anti-CD3 antibody or an antigen binding fragment thereof and said second agent comprises an anti-CD28 antibody or an antigen binding fragment thereof.
15 . The method of claim 11 wherein the patient is afflicted with cancer.
16 . The method of claim 15 wherein the cancer is selected from the group consisting of multiple myeloma, prostate cancer, and chronic lymphocytic leukemia.