What Established Modalities Can Teach Us About Manufacturing In Vivo CAR-T

In vivo CAR-T manufacturing can build on established mRNA-LNP and cell therapy platforms, but targeted delivery introduces distinct development challenges. Experience from mRNA vaccines provides a foundation for scalable particle production, while conventional CAR-T manufacturing offers lessons in linking process controls to biological performance. For in vivo approaches, developers must establish how LNP characteristics influence delivery to T cells, CAR expression, and functional activity. Physicochemical measurements alone cannot demonstrate therapeutic potential, making functional potency strategies essential. Manufacturing decisions made early in development also influence process reproducibility, stability, raw-material selection, analytical controls, and technology transfer. Because transient CAR expression may require repeated administrations, developers must consider how production batches will support dosing schedules and storage requirements.

Platform approaches can reduce development uncertainty by applying established unit operations and manufacturing knowledge, while allowing teams to focus on attributes specific to targeted in vivo delivery. Progress will depend on integrating formulation development, analytical characterization, and process understanding from the outset. Cytiva’s work across RNA-LNP and cell therapy manufacturing, including collaborations supporting LNP-based genome editing and srRNA-LNP development, illustrates how these capabilities can inform emerging programs. Establishing clear relationships between manufacturing conditions and biological performance will help developers prepare in vivo CAR-T candidates for consistent clinical-scale production.