TxCell collaboration presents new proof-of-concept transplantation results with proprietary second-generation CAR-Tregs

  • Results presented at ESOT 2017 in Barcelona
  • Significant effect on mice survival vs. control (p=0.0182) in GvHD model
  • Confirm potential of CAR-Treg technology

VALBONNE, France I September 26, 2017 I TxCell SA (FR0010127662 – TXCL), a developer of cellular immunotherapies based on regulatory T cells (Tregs) for inflammation, autoimmunity and transplantation, today announces details on the new proof-of-concept preclinical data presented at the 18th Congress of the European Society for Organ Transplantation (ESOT), held in Barcelona, Spain, on September 24-27, 2017. The oral presentation made by Prof. Megan Levings describes positive data obtained with proprietary second-generation CAR-Tregs (HLA-A2 CAR-Tregs) in a graft-versus-host disease (GvHD) preclinical model. 

In this study, investigators used the same preclinical GvHD model as was used to evaluate the first-generation murine candidate, which was described in the J. Clin. Invest. 2016 publication[1]. In this model, the second-generation humanized candidate showed similar efficacy as the first-generation murine candidate in preventing GvHD. Similarly to the murine candidate, the humanized candidate showed a significant effect on mice survival vs. control (p=0.0182).

These proprietary second-generation HLA-A2 CAR‑Tregs have a humanized scFv[2] which is expected to minimize the potential for immunogenic clearance of CAR-Tregs cells, a problem known with CAR-T cells bearing a murine scFv. 

The humanized candidate was shown to have higher target specificity compared to the murine candidate. It also appeared that the humanization had no impact on the Treg phenotype nor on Treg functions, such as suppressive effect and cytokine release. 

Developing a second-generation humanized version of our HLA-A2 CAR-Treg candidate is a major step in the TxCell-UBC collaboration. It brings us closer to entering clinical studies with this program,” said Megan Levings, PhD, Professor, Department of Surgery, University of British Columbia (UBC) and Head, Childhood Diseases Research Theme, BC Children's Hospital in Vancouver, Canada. “These new positive proof-of-concept preclinical results confirm the potential of this CAR‑Treg technology to address unmet medical needs in transplant rejection. Both TxCell and UBC are looking forward to continuing to collaborate and present complementary data as we progress.

These new proof-of-concept data demonstrates the progress TxCell has made since the start of our collaboration with UBC less than 12 months ago,” said François Meyer, PhD, Chairman of the Board and Head of Research at TxCell. “The TxCell/UBC collaboration now has a promising proprietary humanized CAR-Treg candidate and we remain on track to initiate a first-in-man study in transplanted patients.”

TxCell and UBC started collaborating on the development of a CAR-Treg-based cellular immunotherapy for the prevention of graft rejection in the context of solid organ transplantation in October 2016. This program is scheduled to start its first-in-man study by the end of 2018, pending appropriate funding.

Presentations details

  • Title: Alloantigen-specific regulatory T-cells generated with a chimeric antigen receptor.
  • Speaker: Megan Levings, PhD, Professor, Department of Surgery, University of British Columbia (UBC) and Head, Childhood Diseases Research Theme, BC Children's Hospital in Vancouver, Canada.
  • Event: 18th Congress of the European Society for Organ Transplantation (ESOT), September 24-27, 2017, Barcelona, Spain.
  • Presentation date & time: September 26, 2017, 11.50 am CEST.

[1] MacDonald KG, Hoeppli RE, Huang Q, Gillies J, Luciani DS, Orban PC, Broady R, Levings MK. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest. 2016, 126(4):1413-1424.

 [2] The single-chain variable fragment (scFv) is the extracellular portion of the CAR, which is responsible for specific targeting of CAR-Treg cells to the diseased tissue of interest. The scFv is typically derived from a monoclonal antibody: the heavy chain variable region and the light chain variable region of said antibody are linked to one another by a peptide to give a single chain, which binds to the desired antigen.

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 a range of autoimmune diseases (both T-cell and B-cell-mediated) including multiple sclerosis, lupus nephritis and bullous pemphigoid, as well as transplant rejection. 

TxCell’s cellular immunotherapies are based on regulatory T lymphocytes (Tregs). Tregs are a T cell population discovered in the 1990’s 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.

SOURCE: TxCell

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