Induction of local immunosuppression in allogeneic cell transplantation by cell-type-specific expression of PD-L1 and CTLA4Ig.

ABSTRACT: Immune rejection has long hindered allogeneic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit drawbacks such as severe adverse effects or elevated tumorigenesis risks. To overcome these limitations, we introduce an innovative approach to induce cell-type-specific immune tolerance in differentiated cells. By engineering human embryonic stem cells, we ensure the exclusive production of the immune inhibitory molecules PD-L1/CTLA4Ig in differentiated cells. Using this strategy, we generated hepatocyte-like cells expressing PD-L1 and CTLA4Ig, which effectively induced local immunotolerance. This approach was evaluated in a humanized mouse model

SUBMITTER: Zhu W 

PROVIDER: S-EPMC10724073 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature