从工厂到患者:体内表达生物制剂作为免疫治疗生产的新范式

Advances in in vivo-expressed biologics are redefining how advanced modality therapeutics can be manufactured, delivered, and rapidly iterated for oncology and immune‑modulating applications. Building on our existing mRNA‑LNP platform for therapeutic antibody expression, we now extend this capability to mRNA‑encoded chimeric antigen receptor (CAR) T cells, establishing an integrated, modular framework for generating functional biologics directly from modified RNA templates. Using clinically validated lipid nanoparticle (LNP) formulations, we have demonstrated efficient translation, secretion, and functional integrity of mRNA‑encoded trastuzumab across in vitro, in vivo PK, and xenograft efficacy models. mRNA‑derived antibody retained antigen specificity and ADCC potency equivalent to recombinant comparators, while in vivo studies showed sustained exposure and superior tumour growth control at reduced doses relative to protein‑infused benchmarks. Additionally, we describe a complementary workflow enabling transient CAR expression in primary human T cells using SM‑102-containing LNPs. Non-viral delivery of HER2‑CAR mRNA resulted in >65% CAR‑positive T cells following expansion, with robust surface expression and preserved viability. Functional cytotoxicity assays demonstrated potent, antigen‑dependent killing of HER2‑expressing tumour targets across a range of effector‑to‑target ratios, confirming that mRNA‑encoded CAR T cells can be rapidly generated and evaluated using standard immunological assay infrastructure. Together, these datasets establish a unified platform for the rapid prototyping, optimisation, and functional validation of in vivo‑expressed biologics. By combining antibody and cellular engineering workflows within a common mRNA‑LNP framework, this approach enables scalable screening of candidate designs, supports mechanism‑of‑action studies, and lays a foundation for future in vivo investigations using targeted LNP technologies. The platform provides a flexible route to accelerate preclinical development of next‑generation biologics, lowering dependency on complex manufacturing and enabling rapid iteration cycles aligned with the emerging field of mRNA‑nanomedicine.