Tcell Tolerance GmbH assigned UGA Biopharma to develop a highly efficient CHO cell line and bioprocess

Hennigsdorf near Berlin, Germany: UGA Biopharma GmbH (UGA), the leading-edge contract developer of cell lines expressing biologics, is developing a new and more efficient CHO-DG44 cell line for German-based startup Tcell Tolerance GmbH (Tcell Tolerance) to express its Palixizumab® antibody.

The new cell line will assist Tcell Tolerance in its quest to develop an innovative therapy to prevent graft-versus-host disease (GvHD), which occurs after allogeneic hematopoietic stem-cell transplantation (HSCT). Tcell Tolerance wants to develop a safer HSCT therapy that can be translated into clinical practice.

The GvHD challenge

Blood stem cells in the bone marrow form human blood cells, including white blood cells (leucocytes), red blood cells (erythrocytes), and platelets (thrombocytes). Where blood stem cell transplantation is needed, e.g. for leukemia, the patient’s immune system first needs to be conditioned, with “old” stem cells depleted and the immune system silenced. This is usually achieved via aggressive high dose chemotherapy. Following this conditioning and stem-cell transplantation, a so-called graft-versus-host disease (GvHD) can occur in which the newly formed white blood cells derived from the implanted stem cells attack different organs of the patient. Clinical symptoms are similar to inflammation, most commonly affecting the skin, intestines, and liver. This immunological reaction can be fatal or lead to severe long-term damage with a permanent need for therapy. The probability of the occurrence of acute GvHD (grade II to IV) after stem cell transplantation is > 30% or 40% for chronic GvHD. Current treatment options for GvHD lead to high costs and a large number of side effects.

Use of Palixizumab® as specific anti-human CD4 antibody

Preclinical studies show that use of Palixizumab® as a specific anti-human CD4 antibody specifically reduces unwanted immune reactions and thus reduce the development of GvHD after stem cell transplantation, while retaining the graft-versus-leukemia (GvL) effect. Palixizumab® is used to treat the transplant rather than the patient, treating stem cells before injection into the patient. The complex after ex-vivo incubation with Palixizumab® and T cells is the ATMP (Advanced Therapy Medicinal Product) Palintra®. Thereby, systemic administration of the antibody can be avoided by merely treating the allogeneic stem cell transplant with the antibody prior to transplantation. Unbound antibody molecules are removed by means of a defined washing process in a closed system. The optimized immune cell therapy is to be tested in a clinical trial to reduce GvHD after HSCT.

UGA Biopharma Cell line development

UGA Biopharma will develop a new and more efficient CHO-DG44 cell line for Tcell Tolerance to express their Palixizumab® antibody.

This work will include:

• Gene design optimized for CHO cells
• Molecular cloning into UGA Biopharma´s proprietary high yield expression vector
• CHO-DG44 transfection and pool generation
• Single cell cloning with Solentims VIPS™ (Verified In-Situ Plate Seeding) instrument for efficient proof of monoclonality by seeding and imaging
• Clone expansion and screening in Ambr® 15 cell culture bioreactors
• Expression stability study conducted in parallel to bioprocess development
• Bioprocess optimization in one liter bioreactors
• Upscaling/Consistency run in five liter bioreactors
• Research Cell Bank (RCB) generation of the lead clone
• Biosafety testing (for sterility and mycoplasma) of the lead clone RCB

Deliverables will include R&D and Commercial license for the use of the CHO-DG44 cell line and UGA’s Expression Technology, along with reports for Cell Line Development, Upstream and Downstream Development, and Analytical Development.

Tcell Tolerance will subsequently coordinate master and working cell bank (MCB/WCB) generation, and Palixizumab® antibody manufacture for clinical trials.

About UGA Biopharma

UGA Biopharma GmbH is an experienced contract research and development organization of biologics and biosimilars with the capabilities to handle all necessary steps from cell line development and bioprocess development to the development of purification strategies and appropriate analytics.

The company supplies its customers in Germany and abroad from its headquarter in Hennigsdorf, near Berlin. Several clients have used UGA products in clinical trials or in products that have received market authorization.

UGA Biopharma GmbH CRDO activities are centered on cell line development for biologics and biosimilars, specializing in the development of stable expressing CHO cell lines and cell media for the production of biologics and biosimilars for biopharmaceutical companies. Typical clients are biopharma manufacturers, research institutions (like universities and research institutes) as well as start-ups and other CROs that need to outsource CLD, upstream, and/or downstream processing.

UGA’s mission is to fulfil customer requests, recognizing industry needs for high titer, high quality and fast delivery timelines, along with robust CHO cell lines. To this end, UGA can deliver cell lines, reaching titers from 4 to 7 g/L, within four months of receiving the originator sequence.

UGA has also developed its proprietary First CHOice® cell culture media and feeds platform to boost the productivity of cell lines. Furthermore, UGA Biopharma GmbH offers ready-to-use biosimilar cell lines, which allow clients interested in biosimilar development fast track access to a highly biosimilar cell line.

Further information at: www.ugabiopharma.com.

About Tcell Tolerance

Tcell Tolerance GmbH, is a startup company (GmbH) founded in February 2017 and based in the heart of Leipzig in Germany.

Tcell Tolerance’s founding mission is to develop an innovative therapy strategy to prevent graft-versus-host disease (GvHD), which forms the greatest risk in allogeneic hematopoietic stem cell transplantation.

Tcell Tolerance is developing a therapy option using the novel Advanced Therapy Medicinal Product (ATMP) Palintra® for allogeneic peripheral blood stem cell transplantation in order to increase the safety of this treatment method, and the translation of this therapy strategy into the clinic.

Learn more at: http://www.tcell-tolerance.de/

Resources

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