CD4⁺ T cells engineered with FVIII-CAR and murine Foxp3 suppress anti-factor VIII immune responses in hemophilia a mice.

ABSTRACT: Although protein replacement therapy provides effective treatment for hemophilia A patients, about a third of severe patients develop neutralizing inhibitor antibodies to factor VIII. Adoptive transfer of regulatory T cells (Tregs) has shown promise in treating unwanted immune responses. In previous studies, transferred polyclonal Tregs ameliorated the anti-factor VIII immune responses in hemophilia A mice. In addition, factor VIII-primed Tregs demonstrated increased suppressive function. However, antigen-specific Tregs are a small fraction of the total lymphocyte population. To generate large numbers of factor VIII-specific Tregs, the more abundant murine primary CD4⁺ T cells were lentivirally transduced ex vivo to express Foxp3 and a chimeric antigen receptor specific to facto

SUBMITTER: Fu RY 

PROVIDER: S-EPMC7655680 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature