Sabine Hünecke, Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Labor für Stammzelltransplantation und Immuntherapien

Flow cytometry enables the analysis of Advanced Therapy Medicinal Products (ATMPs) concerning phenotype, differentiation, and antigen expression intensity. It also facilitates the detection of immune cell functions and the definition of release specifications. Our focus is on five ATMPs: Natural Killer cells, Cytokine Induced Killer cells, Mesenchymal Stroma cells, CAR-T cells, and CAR-NK cells.
For the application of flow cytometry in the quality control of ATMPs, the assay needs to be validated according to the ICH Q2 guideline.

Barbara Lösch, Medigene, Planegg

 Adoptive T cell therapy needs to evolve continuously to overcome the challenges of treating solid tumors and meeting patient needs for long term effective and safe (personalized) TCR-T therapies. Science-based innovations are embedded in an end-to-end platform including multiple, combinable technologies:

  • Effective, specific and safe antigen identification using an in silico screening program to eliminate unwanted epitopes is the basis for development of highly sensitive, highly specific and potent TCRs
  • Utilizing a high throughput robotics platform to find donor TCRs for any antigen/HLA combination accelerates the identification of potent TCRs
  • Creating enhanced inducible TCR products and implementing precision pairing technology to TCRs improve safety and efficacy
  • Adding switch receptors/co-stimulatory switch proteins to arm TCR-T cells against the immunosuppressive tumor microenvironment

Christoph Rücker, ActiTrexx GmbH, Mainz 

Treg are key players in the modulation of immune responses, and control the activation of conventional T cells making them a candidate for cellular therapies in overshooting T cell mediated autoimmune and inflammatory diseases with high unmet medical needs.

The new cellular therapy, activated Treg (ATreg, the active pharmaceutical ingredient of Actileucel) with particularly high suppressor function, has the potential to control pathogenic inflammation. Actileucel has been proven in a preclinical model to be a safe and efficient drug with the potential to minimize excessive T effector cell responses in vitro and in vivo. Actileucel development has led to a tailor made product manufactured in a standardized, economic, semi-automated, GMP compliant process within 24 hours vein-to-vein time.

Christoph Rücker, Janine Schlöder, Niklas Zimmer, Andrea Tüttenberg, Helmut Jonuleit
ActiTrexx GmbH, Mainz

Andreas Traube, Fraunhofer IPA, Stuttgart

ATMPs in general and cell and gene therapies in particular offer enormous potential for treating and curing serious complex diseases. However, the manufacturing processes and quality assurance of sterile products are considerably more complex than for conventional biopharmaceutical drugs. Today's manufacturing processes are highly manual and require a very complex infrastructure. Automated systems for the GMP production of ATMPs are often monolithic and are therefore very inflexible and cannot be scaled efficiently. For these reasons, the costs of production are extremely high today. At the same time, many products have limitations in terms of process stability and product quality. There are thousands of promising ATMPs in the preclinical phase.

Holger Saal, KyooBe, Leinfelden-Echterdingen

A new area in medicine–cell therapies–show promising patient outcomes but still lack commercial success and market access. Why? Most current approaches face challenges in bridging the gap between early clinical trials and efficient large-scale production. In this talk, we present MOSAIC, a novel manufacturing system developed by KyooBe Tech. The aim of MOSAIC is to overcome these challenges by combining modularity, scalability, and parallelization. MOSAIC consists of separate aseptic boxes that can culture cells for different patients and products simultaneously while allowing for both scale-out and scale-up strategies. We describe the design and functionality of MOSAIC and demonstrate its potential for cell therapy development and commercialization.