tLNP103

tLNP103 is an investigational T cell-targeted lipid nanoparticle (tLNP) developed by Sanofi for the in vivo generation of CD19-directed chimeric antigen receptor (CAR) T cells. The therapy utilizes lipid nanoparticles to deliver mRNA encoding a CD19 CAR specifically to endogenous T cells upon systemic administration. This approach aims to replicate the deep B cell depletion and subsequent immune reset observed with autologous ex vivo CAR T cell therapies, but without the need for complex ex vivo manufacturing. By eliminating pathogenic, antigen-experienced B cells and allowing for the repopulation of the immune system with a naïve B cell repertoire, tLNP103 is being explored as a potential treatment for autoimmune diseases. Preclinical studies in non-human primates have demonstrated that multiple doses of tLNP103 can lead to profound B cell depletion in the peripheral blood, lymph nodes, and bone marrow, followed by a molecularly characterized immune reset.