Generation of antigen-specific mature T cells from RAG1^-/-RAG2^-/-B2M^-/- stem cells by engineering their microenvironment.

ABSTRACT: Pluripotent stem cells (PSCs) are a promising source of allogeneic T cells for off-the-shelf immunotherapies. However, the process of differentiating genetically engineered PSCs to generate mature T cells requires that the same molecular elements that are crucial for the selection of these cells be removed to prevent alloreactivity. Here we show that antigen-restricted mature T cells can be generated in vitro from PSCs edited via CRISPR to lack endogenous T cell receptors (TCRs) and class I major histocompatibility complexes. Specifically, we used T cell precursors from RAG1^-/-RAG2^-/-B2M^-/- human PSCs expressing a single TCR, and a murine stromal cell line providing the cognate human major histocompatibility complex molecule and other critical signals for T

SUBMITTER: Chang PC 

PROVIDER: S-EPMC11087257 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature