Ulrich Blache, Fraunhofer IZI, Leipzig

Adoptive immunotherapy using T cells genetically equipped with chimeric antigen receptors (CAR) against CD19 has led to impressive remission rates in cancer patients and six autologous CAR T cell products are market approved for late stage therapy of hematological malignancies. Furthermore, CAR T cell treatment is on its way to also become a second-line and maybe even first-line care option 1. In addition, hundreds of clinical studies2 are ongoing with CAR-T cells, mainly with application in cancer treatment but also non-malignant indications including autoimmune and fibrotic disease are becoming targets for CAR immunotherapy3,4. These great developments in the area of translational medicine leaves us with an unanswered, but under-researched, question: How to produce sufficient numbers of CAR cell products to treat the growing group of patients?5Aside from biological challenges related to tumour-specific efficacy, the mainly manual production of autologous CAR T cells ex vivo severely limits their large-scale application.

Simon Unthan, Biontech, Mainz

Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bispecific checkpoint immuno-modulators, targeted cancer antibodies and small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline.

Philippe-Vollmer-Barosa,Fraunhofer ITEM, Hannover

Human Parainfluenza Virus is the second most abundant pathogen in viral respiratory infections in infants and also has major health implications on immunocompromised high-risk patients such as lung transplant or hematopoietic stem cell transplant recipients. To date, there is no approved specific antiviral clinically available for this infection.
Based on recent successes of RNA-therapeutics, we have developed an inhaled siRNA-based antiviral targeting Parainfluenza infection.

To implement a readily adjustable drug pipeline and foster pandemic preparedness, we set up the iGUARD (integrated Guided Ultrafast Antiviral RNAi Drug development) platform. This includes in silico target prediction and customized screening, infection experiments in vitro, ex vivo (using human Precision-cut lung slices), and in vivo. We further developed an LNP-based formulation for aerosol delivery and tested this in an explanted isolated rat lung model as well as in vivo.

Jantje Gerdes, Evotec International, Göttingen

Compared to small molecule modalities, testing RNA-interference based therapeutics in vivo faces unique challenges. For efficient knockdown, the siRNA must be a complete match to the targeting sequence. However, often the sequence homology between rodent species such as rat or mouse is not high enough to use the same sequence in preclinical animal models and clinical studies leading to the need for additional testing strategies.

Here, we present an approach to identify the most effective GalNAc-modified siRNAs for knockdown of human targets in the mouse liver.

Sascha Karassek, Charles River Laboratories

Potency testing for advanced therapy medicinal products (ATMPs) is both a guideline requirement and a challenge. Often the mechanism of action (MoA) is very complex and may not be fully understood and the reflection with in vivo fate is difficult to demonstrate. With a matrix approach, various aspects of product characteristics can be assessed. On the one hand, transcriptional, translational, and functional levels can be covered, and, on the other hand, various potential MoAs can be addressed. Brief case studies on bioactivity determination for AAV, lentivirus and a plasmid product using the matrix approach are presented.