tLNP103 / Sanofi - LARVOL DELTA

In vivo CD19 CAR T Cells Generated By Targeted Lipid Nanoparticles Induce Deep, Durable, and Robust B cell Depletion Resulting In Immune Reset In Non-Human Primates (ACR Convergence 2026) - "In summary, we demonstrate marked B cell depletion in peripheral blood and a variety of primary and secondary lymphoid tissues, including spleen and lymph node, following dosing with tLNP103 in rhesus macaques. Accordingly, we observe clear signs of a phenotypic and molecular immune reset in these animals, further supporting the depth of B cell depletion enabled by in vivo generated CD19 CAR T cells."

CAR T-Cell Therapy • Lipid Nanoparticle • Preclinical • Hematological Malignancies • Immunology • CD19 • CD8

In Vivo Engineering of CD19 CAR-T Cells Using CD8-Targeted Lipid Nanoparticles: A Potential Breakthrough for Treatment of Autoimmune Disease (ACR Convergence 2026) - "Background/Purpose: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy across autoimmune diseases, for example achieving drug-free remission in refractory systemic lupus erythematosus patients who have previously failed B cell targeted therapies (belimumab or rituximab). CD8-tLNPs enable rapid, efficient in vivo T-cell transfection, generating functional CD19 CAR expression that drives potent B-cell depletion across primary (bone-marrow) and secondary (blood, spleen) lymphoid compartments. This fully synthetic, non-viral, off-the-shelf platform avoids ex vivo manufacturing, complex supply chains, and pre-conditioning chemotherapy, representing a transformative approach with potential for enhanced safety, precise dosing control, and improved accessibility for autoimmune disease management. Human PBMCs were transfected with CD8-targeted LNPs containing CD19-CAR mRNA (tLNP103), control tLNPs containing mCherry mRNA, or left..."

CAR T-Cell Therapy • IO biomarker • Lipid Nanoparticle • Preclinical • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Systemic Lupus Erythematosus • CD19 • CD4 • CD69 • CD8 • GZMB • IFNG • TNFA