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CAR FACTORY is a high-tech, high-output platform for gene-engineered chimeric antigen receptor (CAR) T cell & CAR NK cell products in cancer immunotherapy. Immunotherapy with CAR-modified immune cells is a transformative treatment for selected hematologic malignancies. The therapeutic principle of redirecting the reactivity of immune cells by gene transfer and conferring desired immune cell attributes by gene editing is universally applicable, however at present, the pre-clinical development of novel CAR therapies with specificity other than for the established targets CD19 and BCMA is slow and only few products from the academic development pipeline go into clinical trials in Germany. 

The strategic objective in CAR FACTORY is to streamline and accelerate the pre-clinical development of CAR-modified immune cell therapy in Germany and provide a platform that leverages targets and corresponding CAR immune cell products to subsequent clinical and commercial development. CAR FACTORY will tackle ‘hard-to-treat’ cancers and combine CAR modification with CRISPR/Cas9 gene editing to augment T cell fitness and longevity, T cell trafficking and tumor infiltration, and overcome immune suppressive factors in the tumor environment. To accomplish this ambitious objective, the consortium partners in CAR FACTORY combine interdisciplinary expertise in exploratory research, pre-clinical and clinical development of cellular immunotherapies, target and product validation (partners UKW Würzburg – Hudecek, GUF Frankfurt – Ullrich, IZI Leipzig – Köhl/Schmiedel), virus-free genetic engineering and regulatory affairs (partners IZI – Ivics, UKF Freiburg – Cathomen), manufacturing and scale-up (partners IZI – Köhl and Hudecek). 

An additional key ambition in CAR FACTORY is to deliver optimized immune cell products that comprise a defined blend of CAR T cells and CAR NK cells, and subsequently also CAR macrophages. This strategy will allow conferring sufficient potency to prevent tumor escape and overcome primary and secondary resistance to particular effector mechanisms of each immune cell subset. CAR FACTORY has a strong existing target portfolio centered around ROR-, EGFR-, VEGFR-, B7-, SLAM- and Siglec- antigen families. The CAR FACTORY PIs have brought selected antigens from these target families to pre-clinical proof-of-concept and into clinical development in previous work, and will built on this experience and expertise to establish the CAR FACTORY platform successfully. CAR FACTORY will also explore novel target spaces and will focus on cross-entity targets (i.e. that address several types of cancer) in hematology and oncology. CAR FACTORY will deliver a constant stream of novel targets and immune cell products for clinical translation and adopt ‘external’ target and product candidates from national (and international) partners. To accomplish rapid project output, the consortium has identified two Fast Mover Products that can complete pre-clinical development within two years from project kick-off for deployment into clinical trials. A key performance indicator for CAR FACTORY is to deliver one novel CAR-modified immune cell product per year and overcome the conventional pre-clinical development scheme that is complicated by technological barriers, uncertainties in scale-up and regulatory acceptance. CAR FACTORY provides established GLP, GMP and GCP work flows that adhere to industry standards. CAR FACTORY is supported by an advisory board of patients and patient advocates, experts in adult and pediatric hematology and oncology, experts in intellectual property protection as well as commercial development. 

CAR FACTORY has the ability and ambition to serve as ‘the hub and think tank’ for the pre-clinical development of engineered immune cell therapy in Germany. The CAR FACTORY platform will be highly accessible for academic and private partners to ascertain sustainability beyond the funding scheme supported by German Cancer Aid and broad acceptance in the patient and stakeholder community.