Method to induce and expand therapeutic alloantigen-specific human regulatory T cells in large-scale

Patent metadata

Field	Value
Publication number	US-9480715-B2
Application number	US-201414152269-A
Country	US
Kind code	B2
Filing date	Jan 10, 2014
Priority date	Jun 30, 2008
Publication date	Nov 1, 2016
Grant date	Nov 1, 2016

Abstract

Methods for inducing, expanding, and/or generating alloantigen-specific regulatory T cells. Alloantigen-specific regulatory T cells can be induced, expanded, and/or generated from naive CD4 + CD25 − T cells by using CD40-activated B cells. The regulatory T cells can be human T cells. In one embodiment, the alloantigen-specific human regulatory T cells can be CD4 high CD25 + Foxp3 + regulatory T cells.

First claim

What is claimed is:

1. A method for inhibiting graft versus host diseases (GVHD) with alloantigen specific regulatory T cells, the method comprising:
generating the alloantigen specific regulatory T cells by contacting CD40-activated B cells from a donor of a allograft with naive CD4 + CD25 − T cells from a patient receiving the allograft; and
administering the alloantigen specific regulatory T cells to the patient; wherein
the contacting of donor CD40-activated B cells with patient naïve CD4 + CD25 − T cells is conducted in an absence of exogenenous cytokines.

2. The method of claim 1 , wherein the contacting further comprises contacting donor CD40-activated B cells with naive CD4 + CD25 − T cells from the patient in a ratio of 1:10.

3. The method of claim 1 , further comprising thawing the donor CD40-activated B cells from a cryogenically frozen state.

4. The method of claim 1 , further comprising thawing the naive CD4 + CD25 − T cells from the patient from a cryogenically frozen state.

5. The method of claim 1 , wherein the alloantigen specific regulatory T cells comprise CD4 high CD25 + Foxp3 + regulatory T cells.

6. The method of claim 1 , wherein the alloantigen specific regulatory T cells comprise alloantigen-specific human regulatory T cells.

7. The method of claim 1 , wherein the alloantigen specific regulatory T cells comprise human regulatory T cells and the donor is a human.

8. The method of claim 1 , further comprising obtaining the naïve CD4 + CD25 − T cells from peripheral blood.

9. The method of claim 1 , wherein about 6.4×10 5 to about 1.6×10 7 alloantigen specific regulatory T cells are generated for every about 1×10 6 naive CD4 + CD25 − T cells.

10. The method of claim 1 , wherein about 6×10 6 to about 1.1×10 7 alloantigen specific regulatory T cells are generated for every about 1×10 6 naïve CD4 + CD25 − T cells.

11. A method for inhibiting graft versus host diseases (GVHD) with alloantigen specific human regulatory T cells, the method comprising:
generating the alloantigen-specific human regulatory T cells by contacting CD40-activated B cells from a donor of an allograft with naive CD4 + CD25 − cells from a patient receiving the allograft; and
administering the alloantigen-specific human regulatory T cells to the patient; wherein
the contacting of the donor CD40-activated B cells with the patient naïve CD4 + CD25 − T cells is conducted in an absence of exogenous cytokines.

12. The method of claim 11 , wherein about 6.4×10 5 to about 1.6×10 7 alloantigen-specific human regulatory T cells are generated for every about 1×10 6 naive CD4 + CD25 − T cells.

13. The method of claim 11 , wherein the contacting further comprises contacting donor CD40-activated B cells with naive CD4 + CD25 − T cells from the patient in a ratio of 1:10.

14. The method of claim 11 , wherein the alloantigen-specific human regulatory T cells comprise CD4 high CD25 + Foxp3 + regulatory T cells.

Assignees

• Tu Wenwei
• Lau Yu-Lung
• Lewis David Bram
• Versitech Ltd
• Univ Leland Stanford Junior

Inventors

• Tu Wenwei
• Lau Yu-Lung
• Lewis David Bram

Classifications

• A61K2035/122

  for inducing tolerance or supression of immune responses · CPC title

• C12N2501/23

  Interleukins [IL] · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• C12N2502/11

  blood or immune system cells · CPC title

• C12N2501/52

  CD40, CD40-ligand (CD154) · CPC title