Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

Nat Biotechnol. 2008 Apr;26(4):453-61. doi: 10.1038/nbt1395. Epub 2008 Mar 30.

Abstract

We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Major Histocompatibility Complex / genetics*
  • Major Histocompatibility Complex / immunology*
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Precursor Cells, T-Lymphoid / immunology*
  • Transfection / methods*
  • Transplantation, Homologous