Treatment with autologous T cells that are engineered ex vivo to express a chimeric antigen receptor (CAR) is costly, time-consuming, and requires previous lymphodepletion. Ongoing efforts to simplify autologous CAR-T cell therapy have focused on the development of lipid nanoparticles (LNPs) that deliver a CAR mRNA into CD8+ T cells, to achieve generation of CAR-T cells in vivo. In the New England Journal of Medicine, Gao-Feng Zha, Georg Schett, Zhu Chen and colleagues report the early results of a clinical trial with in vivo CAR-T cell therapy in five individuals with refractory systemic lupus erythematosus (SLE).

The authors used LNPs that carry a portion of a CD8-targeting monoclonal antibody and encapsulate an mRNA encoding a CD19-specific CAR. Use of these LNPs (which were termed HN2301) in vitro and in non-human primates indicated that they can induce both the expression of CD19-CAR on CD8+ T cells and the depletion of CD19-expressing B cells.