TxCell and Inserm Collaborate to Develop New CAR-Tregs in Transplantation and Multiple Sclerosis

Expansion of TxCell’s CAR-Treg platform to develop novel proprietary population of CD8+ regulatory T cells

2 May 2017
Weylan Kiam-Laine
Microbiologist

TxCell SA, a biotechnology company developing innovative, personalized cellular immunotherapies using regulatory T cells (Treg) to treat severe inflammatory and autoimmune diseases as well as transplant rejection, and Inserm Transfert, on behalf of Inserm (French public organization dedicated to human health) and the Nantes University (Nantes, France), have announced the signature of a R&D collaboration agreement. This collaboration agreement complements the December 2016 exclusive worldwide licensing agreement pertaining to a new subset of Treg cells originated in one of the Inserm laboratories.

The agreement announced covers R&D activities to take place between TxCell and the Center for Research in Transplantation and Immunology (CRTI), a center of excellence in the field of transplantation and immunology. The CRTI is a research unit (UMR 1064) affiliated to both Inserm and to the Nantes University. TxCell and the CRTI will collaborate on the development of Chimeric Antigen Receptor (CAR) engineered CD8+Treg cells (CAR‑Tregs). These comprise a proprietary Treg cell population expressing the CD8 marker (CD8+ Tregs). The collaboration will concentrate on the treatment of transplant rejection and autoimmune diseases, specifically focusing on multiple sclerosis. In addition, TxCell and the CRTI will develop a manufacturing process to enable clinical proof-of-concept studies.

The collaboration will expand TxCell’s research efforts, which were focusing so far on engineered CD4+ Treg cells, to explore the therapeutic potential of engineered CD8+ Treg cells in parallel. These CD8+ Tregs are non-cytotoxic and display a unique and highly immunosuppressive mechanism of action, mediated through the release of cytokines with anti-inflammatory and tolerogenic properties.

The transplantation arm of the collaboration announced complements the ongoing collaboration between TxCell and the University of British Columbia (UBC) in Vancouver, Canada. Since October 2016, TxCell and UBC have been working together on the development of a CAR-Treg-based cellular immunotherapy to prevent graft rejection in the context of Solid Organ Transplantation (SOT). The TxCell-UBC collaboration is focused on CAR‑Treg cells made from CD4+ Treg cells.

TxCell is now benefiting from the CRTI’s expertise on these novel CD8+ Treg cells in addition to the intellectual property secured in December 2016,” said François Meyer, Head of Research of TxCell. “Evaluating CAR-CD8+Treg cells in preclinical models of transplantation and autoimmune diseases to confirm their therapeutic potential will continue to push development in key target markets for TxCell.

This collaboration with TxCell will help us set in concrete the clinical development of innovative therapies based on CAR-CD8+Treg cells. We look forward to evaluating with TxCell the potential of these specific CAR-Tregs in the treatment of graft rejection and multiple sclerosis,” said Dr. Carole Guillonneau, CRNS scientist and co‑director of the CRTI team number 2.

TxCell’s expertise in the industrial development of CD4+ Treg cells will be a major asset to move towards a potential use in the clinic of the CD8+ Treg cells we have identified,” added Dr. Ignacio Anegon, INSERM scientist and co‑director of the CRTI team number 2. “This TxCell-CRTI collaboration represents a robust synergy between translational immunotherapy scientists and an experience biotech company.

In December 2016, TxCell gained exclusive worldwide rights to two patent families covering the new type of CD8+ Tregs for all autoimmune diseases and transplantation-related disorders. The CRTI team has already demonstrated the efficacy of these CD8+ Tregs in a number of preclinical models of inflammation, including heart allograft, human skin transplant rejection and graft-versus-host disease (GvHD) in mice with humanized immune systems. In these models, the administration of CD8+ Treg cells has been shown to prevent the occurrence of skin graft rejection and GvHD, respectively.

In addition to the background intellectual property already in-licensed in December 2016, TxCell now also has an exclusive option on programs and products developed under the collaboration agreement.

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