TxCell: First In vivo Proof-of-Concept Data with CD8+ CAR-Treg Presented at FOCIS 2018
- Category: DNA RNA and Cells
- Published on Thursday, 21 June 2018 18:40
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- Significant impact on mice survival and skin graft rejection vs. control in relevant GvHD and skin transplant models
- Confirm potential of novel, proprietary CAR-Treg technology platform to complement TxCell’s other existing Treg platforms
VALBONNE, France I June 21, 2018 I TxCell SA (Paris:TXCL), a developer of cellular immunotherapies based on regulatory T cells (Tregs) for inflammation, autoimmunity and transplantation, today announces that Dr. Carole Guillonneau, PhD, INSERM UMR1064 - Center of Research in Transplantation and Immunology (CRTI, Nantes, France), will present proof-of-concept preclinical data, generated by TxCell and CRTI, at the annual meeting of the Federation of Clinical Immunology Societies (FOCIS 2018) held in San Francisco, USA on June 20 to 23, 2018.
The oral presentation is entitled "Cell therapy with engineered HLA-A2 specific CAR-CD8+ Tregs to avoid transplant rejection". The presentation is the first to deliver data obtained by the TxCell and CRTI collaboration with proprietary CD8+ CAR-Tregs (HLA-A2 CAR-Tregs) in relevant animal models of graft-versus-host disease (GvHD) and skin graft.
In these models, CD8+ CAR-Tregs showed a significant impact on mice survival and delay of skin graft rejection vs. control, respectively. It also was demonstrated that the transduction of a CAR into a CD8+ Treg cell had no impact on the cell phenotype nor on the Treg function, notably its suppressive activity.
The presentation will take place on June 22, 2018, at 2:20 pm local time.
In vivo proof of concept is a major step in the TxCell and CRTI collaboration (please see the About the TxCell and CRTI collaboration and license agreements section below).
“These new proof-of-concept data demonstrate the progress TxCell and CRTI have made since the start of their collaboration only 12 months ago,” said François Meyer, PhD, Chairman of the Board and Head of Research at TxCell. “TxCell now has three CAR-Treg platforms supported by encouraging data. This makes us a clear leader in this emerging field. We expect to start soon the development in humans of the first of these platforms, the CD4+ CAR-Treg platform, with TX200, our lead CAR-Treg program targeting HLA-A2 for the prevention of chronic rejection after organ transplantation. TxCell will continue in parallel to invest in its earlier stage CD8+ Treg and Tr1 platforms. This will give the best chance to TxCell to select the most appropriate approach for patients in areas of significant unmet medical need.”
About the CD8+ Tregs:
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 properties1,2. As a result, CD8+ Tregs could offer both a different and complementary approach to treat inflammatory disorders, including autoimmunity and transplant rejection.
CRTI, or Center of Research in Transplantation and Immunology, is a research unit (UMR 1064) affiliated to both Inserm, a French public organization dedicated to human health, and to the Nantes University (Nantes, France).
The CRTI team, which is led by Ignacio Anegon and Carole Guillonneau, has already demonstrated the efficacy of these CD8+ Treg cell population in several 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.
About the TxCell and CRTI collaboration and license agreements:
On December 8, 2016, TxCell was granted an exclusive worldwide license to two patent families filed by CRTI. These patents cover a new type of regulatory T cells (Tregs) that express the CD8 marker. This is in contrast to traditionally known Tregs that express CD4 such as the type 1 Tregs and FoxP3+ Tregs. The patents licensed by TxCell that cover CD8+ Treg cells also cover CAR-Treg cells made from these CD8+ Treg cells.
On May 2, 2017, TxCell announced it has entered into a collaboration agreement with CRTI on the development of Chimeric Antigen Receptor (CAR) engineered CD8+ Treg cells (CAR-Tregs). The collaboration will concentrate on the treatment of transplant rejection and autoimmune diseases, specifically focusing on multiple sclerosis. In addition, TxCell and CRTI will develop a manufacturing process to enable clinical proof-of-concept studies.
About TxCell – www.txcell.com
TxCell is a biotechnology company that develops platforms for innovative, personalized T cell immunotherapies for the treatment of severe inflammatory and autoimmune diseases with high unmet medical need. TxCell is targeting transplantation as well as a range of autoimmune diseases (both T-cell and B-cell-mediated), such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases or inflammatory skin diseases.
TxCell’s cellular immunotherapies are based on regulatory T lymphocytes (Tregs). Tregs are a T cell population discovered in the nineties for which anti-inflammatory properties have been demonstrated. Contrary to conventional approaches based on non-specific polyclonal Tregs, TxCell is exclusively developing engineered antigen-specific Tregs, where the antigen specificity is brought by a Chimeric Antigen Receptor (CAR) (CAR-Treg cells).
Based in Sophia-Antipolis, France, TxCell is listed on Euronext Paris and currently has 46 employees.
1 Bézie S, Picarda E, Ossart J, Tesson L, Usal C, Renaudin K, Anegon I, Guillonneau C. IL-34 is a Treg-specific cytokine and mediates transplant tolerance. J Clin Invest. 2015 Oct 1;125(10):3952-64.
2 Picarda E, Bézie S, Venturi V, Echasserieau K, Mérieau E, Delhumeau A, Renaudin K, Brouard S, Bernardeau K, Anegon I, Guillonneau C. MHC-derived allopeptide activates TCR-biased CD8+ Tregs and suppresses organ rejection. J Clin Invest. 2014 Jun;124(6):2497-512.