Process Systems Engineering in Precision Medicine: Opportunities in Autologous CAR-T Therapy.

Autologous chimeric antigen receptor (CAR)-T therapies have given hope to many cancer patients whose other lines of treatment have failed. Unfortunately, limited manufacturing capability has resulted in many patients dying while on a waitlist. Similarly, since clinical trial treatments are personalized, it is difficult to treat many patients simultaneously, resulting in longer clinical trials. Therapeutic production often takes over 4 weeks, so a product failure means that a patient may need to wait another month for treatment, putting them at severe risk for disease progression. The labor-intensive manufacturing process has led to therapeutic costs of roughly $500,000 per treatment, which can be reduced by better automation and shorter manufacturing times. The goals of this article are to review CAR-T therapeutics development, manufacturing, and treatment, and to encourage the development of data analytics-based multi-scale decision support tools for all humans "in the loop." A systems approach is needed since prior treatments and current state of health (including the immune system and microbiota), initial cell quality, manufacturing failure, bridging and lymphodepletion therapy before infusion, and supply chain management, all impact treatment success. Continuous updates as more patient data are made available can lead to better treatment recommendations and outcomes.