Single injection of modified self-amplifying RNA encoding a CD19 bispecific T cell engager mediates long-term malignant B cell clearance

Apr 27, 2026bioRxiv : the preprint server for biology

One injection of modified RNA that activates T cells targeting CD19 supports long-term removal of cancerous B cells

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mRNA Technology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A single intravenous injection of the saRNA-BiTE system eradicates malignant cells and prevents disease recurrence for 3 months in an acute lymphoblastic leukemia model.

saRNA-BiTE targets CD19 and induces prolonged, antigen-specific destruction of target cells.
This novel system maintains more stable systemic levels compared to traditional protein BiTE or mRNA-BiTE.
saRNA-BiTE provides functional BiTE expression for 6 weeks after administration without initial burst exposure.
The approach utilizes self-amplifying RNA technology for durable protein production, potentially improving patient access.

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Bispecific T cell engagers (BiTEs) are a novel cancer immunotherapy modality that achieves significant clinical success. However, conventional single-chain variable fragment (scFv)-based BiTE therapy requires continuous intravenous infusion due to BiTE's short half-life, limiting patient access and increasing healthcare cost. Self-amplifying RNA (saRNA), an emerging RNA technology, enables durable protein production. Here, we report a 5-methylcytidine (m5C)-modified saRNA encoded BiTE system (saRNA-BiTE) targeting CD19. saRNA-BiTE induces prolonged, antigen-specific target cell lysis. In an acute lymphoblastic leukemia rechallenge model, a single intravenous injection of saRNA-BiTE formulated in lipid nanoparticles eradicates malignant cells and prevents disease recurrence for 3 months. saRNA-BiTE maintains more stable systemic level than protein BiTE or mRNA-BiTE without generating an initial burst BiTE exposure and affords functional BiTE expression for 6 weeks post administration. This work establishes saRNA-BiTE as a robust platform for extendedBiTE expression with enhanced long-term efficacy and facile production. in situ in vitro in situ