Induction of long-term tolerance to a specific antigen using anti-CD3 lipid nanoparticles following gene therapy.

ABSTRACT: Development of factor VIII (FVIII) inhibitors is a serious complication in the treatment of hemophilia A (HemA) patients. In clinical trials, anti-CD3 antibody therapy effectively modulates the immune response of allograft rejection or autoimmune diseases without eliciting major adverse effects. In this study, we delivered mRNA-encapsulated lipid nanoparticles (LNPs) encoding therapeutic anti-CD3 antibody (αCD3 LNPs) to overcome the anti-FVIII immune responses in HemA mice. It was found that αCD3 LNPs encoding the single-chain antibodies (Fc-scFv) can efficiently deplete CD3⁺ and CD4⁺ effector T cells, whereas αCD3 LNPs encoding double-chain antibodies cannot. Concomitantly, mice treated with αCD3 (Fc-scFv) LNPs showed an increase in the CD4⁺CD25⁺

SUBMITTER: Chen CY 

PROVIDER: S-EPMC10618827 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature