Methods of culturing t cells and uses of same

Patent metadata

Field	Value
Publication number	US-11932871-B2
Application number	US-201816490568-A
Country	US
Kind code	B2
Filing date	Mar 2, 2018
Priority date	Mar 2, 2017
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

Methods of culturing T cells are provided. Accordingly there is provided a method of culturing T cells comprising culturing T cells in the presence of a T cell stimulator, an exogenous CCL21 and an exogenous ICAM1, thereby culturing the T cells. Also provided are cell cultures, isolated T cells and uses of same.

First claim

What is claimed is:

1. A method of culturing T cells, the method comprising culturing T cells in a culture vessel in the presence of a T cell stimulator, an exogenous CCL21 and an exogenous ICAM1, thereby culturing the T cells, wherein each of said CCL21 and ICAM1 are immobilized to a solid support, wherein said T cell stimulator is an antigen-specific stimulator comprising a dendritic cell loaded with an antigen, wherein said immobilized CCL21 and ICAM1 are attached to said culture vessel, and wherein said T cells comprise engineered T cells transduced with a nucleic acid encoding a T cell receptor (TCR) or a chimeric antigen receptor (CAR).

2. The method of claim 1 , wherein said culturing is effected for 3-7 days.

3. The method of claim 1 , further comprising adding a cytokine to the culture.

4. The method of claim 3 , wherein said T cells comprise CD4 + T cells and said cytokine is IL-6.

5. The method of claim 3 , wherein said T cells comprise CD8 + T cells and said cytokine is not IL-6.

6. The method of claim 1 , wherein said T cells comprise CD4 + T cells.

7. The method of claim 1 , wherein said T cells comprise CD8 + T cells.

8. A method of producing engineered T cells, the method comprising transducing T cells with a nucleic acid encoding an expression product of interest and further comprising culturing said T cells in a culture vessel in the presence of an exogenous chemokine, an exogenous adhesion molecule and a T cell stimulator, thereby producing the engineered T cells, wherein said chemokine is CCL21, and said adhesion molecule is ICAM1, and wherein each of said chemokine and adhesion molecule are immobilized to a solid support, wherein said T cell stimulator is an antigen-specific stimulator comprising a dendritic cell loaded with an antigen, wherein said immobilized CCL21 and ICAM 1 are attached to said culture vessel, and wherein said expression product of interest is a T cell receptor (TCR) or a chimeric antigen receptor (CAR).

9. The method of claim 1 or claim 8 , wherein said antigen is a cancer antigen.

10. The method of claim 1 or claim 8 , wherein the T cells seeding concentration in the culture is less than 5×10 4 cells/ml culture medium.

Assignees

• Yeda Res & Dev
• Medical Res Infrastructure & Health Services Fund Tel Aviv Medical Ct

Inventors

• Geiger Benjamin
• Friedman Nir
• Lieber Shimrit
• Eshhar Zelig
• Waks Tova
• Globerson Levin Anat

Classifications

• A61K40/4205

  Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4 · CPC title

• A61K40/42

  Cancer antigens · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title

• A61K40/19

  Dendritic cells · CPC title