Comparison of ex vivo engineering and in vivo programming strategies for CAR‐M therapies.
Ex vivo engineering In vivo programming
Basic principle Macrophages are isolated, engineered, characterized, and reinfused. CAR‐encoding payloads are delivered directly into the body to program endogenous macrophages in situ.
Safety profiles Possible off‐target tissue accumulation after infusion; integrating vectors pose insertional mutagenesis risks. Avoids live‐cell infusion; can use non‐integrating mRNA. Off‐target delivery remains a concern.
Controllability Cell dose, CAR expression, and initial phenotype can be predefined. Vehicle dose is controllable, but the number, location, and persistence of generated CAR‐M are less predictable.
Manufacturing complexity High complexity and cost; requires cell isolation, engineering, expansion, and quality control. Low complexity; avoids live‐cell processing and supports scalable off‐the‐shelf production.
Clinical applicability Suitable when precise product control is required, when endogenous macrophages are depleted, or when durable CAR expression is desired. Suitable for acute/subacute conditions, repeated transient intervention, or diseases with sufficient endogenous macrophage pools.
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