Pharmaceuticals
Platform for Boosting Yield and Activity of Therapeutic T Cells (No. T4-1810)

5665
Overview

Production of large quantities of T cells is an essential demand for the development of immunotherapies. However, ex-vivo culturing of T-cells is very inefficient, resulting in high cell death rates. The current technology offers unique, optimized conditions that allow increased T-cell proliferation while enhancing their functionality.

Background and Unmet Need
Culturing and expanding T cells ex-vivo while retaining their functionality is an essential requirement when developing cutting-edge immunotherapies. A significant problem frequently faced by the industry is the low number of T cells available for adoptive immunotherapy and the difficulty to retain their functionality following extended incubation and expansion ex vivo. Specifically, T-cell cultivation commonly leads to short-term cell proliferation, followed by gradual loss of functionality, growth arrest, and increased cell death. Consequently, there is a strong need to develop novel technologies that could increase T-cell proliferation while maintaining or even enhancing their functionality.
The Solution

The team of Prof. Geiger identified a set of conditions that mimic the natural immune niche resulting in increased T cell proliferation and functionalization in vitro.

Technology Essence

The Geiger research team discovered that coating the culturing vessels with CCL21 and ICAM1 created a synthetic immune niche, leading to a significant increase in the growth of murine CD4+T cells. The addition of IL6 to the culture medium further increased the number of viable CD4+ T, providing an approach for efficiently generating antigen-specific immunotherapeutic CD4+ T cells1. Similarly, the team found that substrate-immobilized CCL21 and ICAM1 stimulate the expansion of murine cytotoxic CD8+ T-cells. Moreover, these conditions also elevate the cellular levels of granzyme B expressed in these cells, resulting in an improved killing of cultured cancer cells and markedly elevated tumor-suppressive activity in vivo.2 To conclude, the new combination used by the team resulted in a considerable increase in the number and function of viable T cells after a few days in culture.

Advantages and Advantages
  • Expanding large quantities of CD4+ and CD8+ T cells ex-vivo (for example tumor infiltrating T cells (TILs) from biopsies) to facilitate cancer immunotherapy applications
  • Producing highly functional antigen-specific CD8+ T cells for tumor suppression.
  • Capacity to stimulate functional CAR-Ts and TILs.
  • Specific – Co-culturing with antigen loaded dendritic cells allows antigen-specific T cell expansion (e.g. cancer neo-antigen T cells).
Development Status

The team of Prof. Geiger tested numerous conditions on murine CD4+ and CD8+ T cells to define the optimal "synthetic immune niche" for growing said cells. The team has performed in vitro tests to increase CD4+ and CD8+ T cell expansion and function and has further tested the cells in vivo in an adoptive immunotherapy animal model. Lastly, the team has validated the SIN platform in human CAR-Ts and TILs.

 

References

1. Adutler-Lieber, S. et al. Substrate-bound CCL21 and ICAM1 combined with soluble IL-6 collectively augment the expansion of antigen-specific murine CD4+ T cells. Blood Adv. 1, 1016–1030 (2017).

Adutler-Lieber, S., Friedman, N. & Geiger, B. Expansion and Antitumor Cytotoxicity of T-Cells Are Augmented by Substrate-Bound CCL21 and Intercellular Adhesion Molecule 1. Front. Immunol. 9, 1303 (2018).

Patent Status: 
USA Published: Publication Number: 2020-0071669-A
Associate Professor Nir FRIEDMAN

Nir Friedman

Biology
Immunology
All projects (1)
Extension Service Benjamin Geiger

Benjamin Geiger

Faculty of Biology
Immunology
All projects (2)
Contact for more information

Dr. Elik Chapnik

Sr. Director of Business Development, Life Science

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