Design and characterization of novel nanobody-conjugated lipid nanoparticles for targeted in vivo CAR-T therapy

Yanjie Huang – post doc, Karolinska Institute; Oliver Hayes – post doc, Karolinska Institute; Ruben De Coen – Senior Manager, eTheRNA Immunotherapies; Sabah Kasmi – Senior Scientist, eTheRNA Immunotherapies; Stefaan De Koker – VP Technology & Innovation, eTheRNA Immunotherapies; Samir El Andaloussi – professor, Karolinska Institute

Introduction: Lipid nanoparticles (LNPs) have emerged as a promising platform for in vivo CAR-T therapy by enabling direct delivery of CAR-encoding nucleic acids to T-cells inside the patient, bypassing the need for complex and expensive ex vivo cell manufacturing [1]. However, effective LNP targeting remains challenging due to the LNP tendency to accumulate in the liver. Here we aimed to identify LNP compositions allowing for increased T-cell delivery and further boosted the specificity by decorating with anti-CD8 nanobodies. Moreover, we aimed to evaluate the effect of nanobody density on LNP targeting and delivery. The outline of the project is depicted in Fig. 1.