Cell and gene therapies, particularly based on CAR-T, 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 than desired 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, often putting them at risk for disease progression. The labor-intensive manufacturing process has led to costs that are roughly $500,000 per treatment. 

            The major objective of our effort is to develop advanced automated analytics and decision-making techniques to reduce clinical trial and treatment time and increase the number of patients that can be treated simultaneously. A systems approach is taken, since patient prior treatments and current state of health, initial cell quality, lymphodepletion and possible bridging therapy before infusion, and supply chain management, all impact treatment success. The microbiota is important since patients who have taken broad-spectrum antibiotics before receiving CAR-T cell therapy have less microbiome diversity and poorer treatment outcomes. Post-infusion patient monitoring using wearables can enable a safer and more rapid transition to out-patient status.        

            We stress that “manufacturing” is more than the multiple steps from aphaeresis to infusion, but includes detailed information about the patient, prior and on-going treatments, cell phenotype, etc. A major challenge is reducing T-cell "exhaustion" and several solutions have been proposed. Different bioreactors for T-cell expansion can lead to different T-cell differentiation states and thus reduced exhaustion and better efficacy. Our initial focus is on the approved FDA CAR-T therapies for hematological cancers because there are patient outcome results available, but we also discuss on-going efforts to treat solid tumors.