Mapping CAR T Cell Therapy: Strategies to Maximize Expansion, Persistence, Trafficking & Efficacy/Mapping CAR T: Maximizing Expansion, Persistence & Trafficking

Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for select hematologic malignancies, yet inconsistent expansion, limited persistence, suboptimal trafficking, and antigen heterogeneity constrain broader, durable benefit. This presentation surveys engineering and translational strategies that address these barriers. We will discuss methods to augment in vivo expansion, such as antigen-bridging vaccination concepts, and programs that preserve stem-like and resident-memory states to sustain long-term function. Approaches to improve trafficking and activity within solid tumors, including locoregional delivery and microenvironment-aware designs, will be highlighted. Finally, we will connect these biological principles to emerging preclinical and clinical data, outlining pragmatic paths to safer, more effective CAR T products across indications. Attendees will leave with a framework for selecting and combining interventions that enhance potency while mitigating toxicity and for translating these insights into next-generation cell therapies.

Learning Objectives:

1. Describe mechanisms that limit CAR T-cell expansion, persistence, and trafficking, and how these impact clinical outcomes.

2. Evaluate strategies (e.g., antigen-bridging vaccination, maintenance of stem-like/TRM programs, locoregional delivery) to enhance efficacy and durability.

3. Identify practical considerations for translating these approaches into clinical protocols while minimizing toxicity.