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Anti-TOSO CAR T Cells - Highly selective immunotherapeutic approach to CLL treatment

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Angebotsbeschreibung

Ref.-Nr. 4417

Background

Cancer-immunotherapy is currently gaining interest thanks to novel genetic engineering technologies. The most promising approach is the chimeric antigen receptor (CAR) technique for redirecting hereby modified T cells against cancer-associated antigens.

TOSO (also known as Faim 3) is a type I transmembrane protein that is involved in Fas-induced apoptosis. It is overexpressed on chronic lymphatic leukemia (CLL) cells, whereas the level of expression is correlated with the aggressiveness of the disease. In contrast, TOSO is only weakly expressed on normal lymphocytes. This expression profile qualifies TOSO as target antigen for immunotherapeutic anti-leukemia approaches by means of CAR T cells.

Invention

The herein presented CAR constitutes of a B cell-derived single chain antibody fragment (scFv) directed against TOSO. This ectodomain is fused with a co-stimulatory CD28 T cell activation domain, finally followed by a CD3ζ domain. The receptor is introduced into allogenic or autologous peripheral blood T cells by retroviral gene transfer.

Cell-based assays show high killing specificity of the anti-TOSO CAR T cells against CLL cells, whereas normal B cells remain intact. The discrimination is strongly improved in comparison to previously engineered anti-CD19 CAR T cells that are currently used in clinical studies.

Commercial Opportunities

The described anti-TOSO CAR T cells have a strongly improved selectivity of target cell killing. The reduction of adverse effects on normal cells provides a competitive advantage against all other CAR T cell approaches that are currently on the market.

Current Status

Functional data have been generated in cell-based assays with allogenic and autologous CAR T cells showing selectivity and efficiency of target cell killing activity (original data available on a confidential basis).

A European patent application and a US patent application are pending.

On behalf of the University of Cologne, PROvendis offers a patent license as well as a research collaboration with licensing option.

Relevant Publication

Chmielewski M, Hombach AA, Abken H. Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells. Front. Immunol. 2013; 4: 371.

Cheadle EJ, et al. Chimeric antigen receptors for T-cell based therapy. Methods Mol. Biol. 2012; 907:645-66.


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Kordula Kruber
+49.208 94105-30
kk@provendis.info

Kordula Kruber

Dieses Angebot

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PROvendis GmbH · Schloßstr. 11 – 15
D – 45468 Mülheim an der Ruhr
T +49 (0)208 94105-0 · kontakt@provendis.info

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