Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

Journal: 
PLoS One
Publication Year: 
2009
Authors: 
Scott G Kitchen , Michael Bennett , Zoran Galic , Joanne Kim , Qing Xu , Alan Young , Alexis Lieberman , Aviva Joseph , Harris Goldstein , Hwee Ng , Otto Yang , Jerome A Zack
Public Summary: 
Scientific Abstract: 
There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

© 2013 California Institute for Regenerative Medicine