Imagining the Cell Therapist: Future CAR T Cell Monitoring and Intervention Strategies to Improve Patient Outcomes

Chimeric antigen receptor (CAR) T cell therapy is now approved for the standard of care treatment of several types of relapsed or refractory hematologic malignancies. Future advances may extend cellular therapies to solid tumors or even non-malignant diseases. As patient need grows, a clinical specialty of "cell therapy" may emerge. Here, we envision the needs of a clinical cell therapist to monitor and intervene upon patients receiving cell therapies. These include: (1) monitoring patient T cell quality and the host immune environment to ensure optimal timing for cell therapy. (2) Tumor antigen profiling to personalize CAR T cell targeting. (3) Real-time monitoring of CAR T cells and circulating tumor DNA to modulate CAR T cell activity to maximize tumor eradication while mitigating toxicity. (4) Monitoring of CAR rejection and anti-CAR immunity posttreatment to inform re-dosing and subsequent cell therapy strategies. Armed with these tools, the future Cell Therapist may optimize and personalize treatment to avoid toxicity and improve efficacy universally across CAR designs.