From pipeline expansion to manufacturing maturity: China's role in the global in vivo CAR-T landscape

The ex vivo manufacturing bottleneck in chimeric antigen receptor T cell (CAR-T) therapy has spurred a global race toward in vivo approaches that engineer CAR-Ts directly inside patients. In this context, Chinese biotechnology clusters are emerging as significant industrial centers, reflected in pipeline data (NextPharma database, accessed January 2026. Assets were filtered for “in vivo CAR-T” modality and “active” development status), showing that the volume of active in vivo CAR-T assets under development in China has recently surpassed that of the United States and Europe (Figure 1A). While pipeline volume does not equate directly to clinical or commercial leadership, it suggests an integrated supply chain ecosystem tackling vector production challenges.

Technological pathways and strategic positioning

Viral vector pathway: Pursuing durability with manufacturing constraints

Viral vectors, particularly lentivirus, enable stable genomic integration of CAR transgenes, potentially enabling long-term CAR expression that may be advantageous for indications requiring sustained responses. However, this approach faces substantial manufacturing and safety hurdles, including pre-existing immunity to viral envelope proteins, theoretical risks of insertional mutagenesis, and the absence of reliable pharmacologic “off-switches” for toxicity management.

Shenzhen Pregene Biopharma has pursued this pathway by collaborating with Belgium’s EsoBiotec to develop ESO-T01, an in vivo CAR-T therapy targeting B cell maturation antigen (BCMA) to treat multiple myeloma. ESO-T01 utilizes an engineered nanobody-displaying lentiviral platform for targeted T cell transduction and has entered phase 1 clinical trials.1 The scientific rationale for surface-displayed ligand targeting is established, but in vivo selectivity and off-target rates await clinical characterization.

Researchers at Westlake University developed an adeno-associated virus (AAV)-mediated in vivo CAR delivery system targeting the T cell surface marker CD62L. This represents a foundational innovation in targeting specificity rather than mere process improvement. Preclinical data suggest that this approach achieves T cell-specific delivery while mitigating hepatotoxicity.2 Unlike integrating lentiviruses, AAV predominantly maintains episomal persistence. While this theoretically offers an intermediate duration profile, AAV episomes are diluted during T cell proliferation, making long-term persistence in this rapidly dividing cell population uncertain.