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

Scott G. Kitchen, Michael Bennett, Zoran Galić, Joanne Kim, Qing Xu, Alan Young, Alexis Lieberman, Aviva Joseph, Harris Goldstein, Hwee Ng, Otto Yang, Jerome A. Zack

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Article numbere8208
JournalPloS one
Volume4
Issue number12
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kitchen, S. G., Bennett, M., Galić, Z., Kim, J., Xu, Q., Young, A., Lieberman, A., Joseph, A., Goldstein, H., Ng, H., Yang, O., & Zack, J. A. (2009). Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice. PloS one, 4(12), [e8208]. https://doi.org/10.1371/journal.pone.0008208