Toward Rapid, Widely Available Autologous CAR-T Cell Therapy - Artificial Intelligence and Automation Enabling the Smart Manufacturing Hospital.

CAR-T cell therapy is a promising treatment for acute leukemia and lymphoma. CAR-T cell therapies take a pioneering role in autologous gene therapy with three EMA-approved products. However, the chance of clinical success remains relatively low as the applicability of CAR-T cell therapy suffers from long, labor-intensive manufacturing and a lack of comprehensive insight into the bioprocess. This leads to high manufacturing costs and limited clinical success, preventing the widespread use of CAR-T cell therapies. New manufacturing approaches are needed to lower costs to improve manufacturing capacity and shorten provision times. Semi-automated devices such as the Miltenyi Prodigy ^® were developed to reduce hands-on production time. However, these devices are not equipped with the process analytical technology necessary to fully characterize and control the process. An automated AI-driven CAR-T cell manufacturing platform in smart manufacturing hospitals (SMH) is being developed to address these challenges. Automation will increase the cost-effectiveness and robustness of manufacturing. Using Artificial Intelligence (AI) to interpret the data collected on the platform will provide valuable process insights and drive decisions for process optimization. The smart integration of automated CAR-T cell manufacturing platforms into hospitals enables the independent manufacture of autologous CAR-T cell products. In this perspective, we will be discussing current challenges and opportunities of the patient-specific but highly automated, AI-enabled CAR-T cell manufacturing. A first automation concept will be shown, including a system architecture based on current Industry 4.0 approaches for AI integration.
Competing Interests: JJ was employed by ORTEC BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Companies Fraunhofer Institute for Cell Therapy and Immunology IZI, University College London, Foundation for Research and Technology (FORTH)-Hellas, SZTAKI, University Clinics Würzburg, Aglaris Cell SL, Sartorius Cell Genix GmbH, Fundació Clínic per a la Recerca Biomèdica, IRIS Technology Solutions, Red Alert Labs, Panaxea b.v., ORTEC b.v. were involved in the elaboration of the idea of the paper, the reviewing and the decision to submit the paper.
(Copyright © 2022 Hort, Herbst, Bäckel, Erkens, Niessing, Frye, König, Papantoniou, Hudecek, Jacobs and Schmitt.)