Reprogramming CD22 CAR-T cells in vivo using CD8-targeted mRNA-LNPs to treat hematological malignancies

Molecular Therapy 2026 Open access

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Authors: Viktor T. Lemgart, Andrew J. Sawyer, William Kuhlman, Aaron P. Griset, Mir M. Ali, Allison Caron, Dharini Shah, Tiffany Le, Laura Strauss, Jing Jiao, Francis J. Descamps, Sampa Maiti
+26 more Michael T. Monte, R.D. Augspurg, Eyoung Shin, Ernesto Ráez Luna, Pankaj Agrawal, Jan Pype, Olga Lihoradova, James T.H. Cao, Brandon Quido, Laura Powers, Fazila Nasimi, Jacob Scantland, Kavana Girish, Rasika D Kunden, Jennifer Richards, Samantha Stewart, Seunghee Lee, Garry Cuneo, Janina Schwarte, Christian Mueller, Christopher M. Borges, Austin W. Boesch, Valeria R. Fantin, Ulrik B. Nielsen, Donald Shaffer, Daryl C. Drummond
DOI: 10.1016/j.ymthe.2026.02.020
Cited by: 10
References: 85

Abstract

cells, enabling transient functional CAR expression in vitro and in vivo. Our targeted LNP formulation allows for repeated dosing and minimizes mRNA expression in off-target cells. Furthermore, in a humanized Nalm6 tumor mouse model, non-stimulated T cells reprogrammed in vivo inhibit tumor cell growth. Our platform is a flexible and broadly applicable CAR-T treatment for hematologic malignancies, which promises to be adaptable to other diseases.

Fields of Study & Subjects

CAR-T cell therapy research Immunotherapy and Immune Responses Virus-based gene therapy research

Publication details

Journal / source
Molecular Therapy
Publisher
Elsevier BV
Volume
34
Issue
5
Pages
2621–2636
Publication date
14 February 2026
Language
EN