Engineering Antiviral T Cell Immunity through Stem Cells and Chimeric Antigen Receptors

摘要

The HIV-specific cytotoxic T lymphocyte (CTL) response is a critical component in controlling HIV replication and is an important part of the ultimate failure to eradicate the virus. Disclosed herein are methods for genetically enhancing the HIV-specific CTL response to allow long-term viral suppression or viral clearance. Human hematopoietic stem cells (HSCs) were genetically modified such that they differentiate into mature CTLs that will kill HIV infected cells. As disclosed herein, the functional effector cells are not human leukocyte antigen (HLA)-restricted. As disclosed herein, stem cells are transduced with non HLA-restricted chimeric antigen receptors (CARs) that allow the recognition of HIV or HIV infected cells when expressed by a CTL.

主权项

1. A recombinant progenitor cell which comprises
a stem cell transduced with a vector containing a nucleic acid molecule which encodes a chimeric antigen receptor (CAR) specific for a virus or an epitope thereof, wherein the recombinant progenitor cell is capable of differentiating into a functional effector cell.