Programming of antigen-specific CTLs from induced pluripotent stem cells for tumor protection (156.1) Academic Article uri icon

abstract

  • Abstract Generation of highly reactive antigen(Ag)-specific CTLs derived from induced pluripotent stem(iPS) cells can provide an unlimited source of functional CTLs that can be used for adoptive immunotherapy. The iPS cell-derived T cells have the advantages of averting potential immune rejection, as well as circumventing ethical and practical problems associated with other types of stem cells. Previously we demonstrated that iPS cells are able to differentiate into progenitor T cells in vitro by the stimulation of Notch ligand Delta-like 1 (DL1) over-expressed on OP9 bone marrow stromal cells. Full maturation of iPS cells was observed upon adoptive transfer into RAG1-deficient mice. Here we show that iPS cells differentiate into functional CTLs in vivo after over-expressing MHC I-restricted Ag-specific T cell receptors (TCRs). In this study, murine iPS cells are genetically modified with OVA specific, MHC-I restricted TCR (OT-I) by retroviral transduction. We demonstrate that after adoptive transfer into recipient mice, the majority of OT-I/iPS cells undergo differentiation into CD8+ CTL. In vivo developed TCR-transduced iPS cells are able to respond to ex vivo peptide stimulation and secrete IL-2 and IFN-. Moreover, adoptive transfer of TCR-transduced iPS cells results in the infiltration of OVA-reactive CTLs into tumor tissues and protection of animals from tumor challenge. Our results provide a novel approach for generating Ag-specific T lymphocytes for T cell-based therapies.

published proceedings

  • The Journal of Immunology

author list (cited authors)

  • Lei, F., Haque, R., & Song, J.

citation count

  • 0

complete list of authors

  • Lei, Fengyang||Haque, Rizwanul||Song, Jianxun

publication date

  • April 2011