bioRxiv : the preprint server for biologyApr 27, 2026

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

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A single lipid-nanoparticle dose of modified saRNA encoding a CD19 BiTE produced prolonged BiTE expression and cleared malignant B cells in a leukemia rechallenge model.

Evidence

This preclinical RNA-platform study tested m5C-modified saRNA-BiTE in vitro and in an acute lymphoblastic leukemia rechallenge model, with expression lasting 6 weeks and recurrence prevented for 3 months.

Caveat

The findings come from preclinical models, so clinical safety, immune effects, dosing control, and durability in patients are unknown.

Simplified

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