Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors Journal Article


Authors: Zakrzewski, J. L.; Suh, D.; Markley, J. C.; Smith, O. M.; King, C.; Goldberg, G. L.; Jenq, R.; Holland, A. M.; Grubin, J.; Cabrera-Perez, J.; Brentjens, R. J.; Lu, S. X.; Rizzuto, G.; Sant'angelo, D. B.; Riviere, I.; Sadelain, M.; Heller, G.; Zúñiga-Pflücker, J. C.; Lu, C.; van den Brink, M. R. M.
Article Title: Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors
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. © 2008 Nature Publishing Group.
Keywords: transplantation, homologous; nonhuman; neoplasms; t lymphocyte; animal cell; mouse; animals; mice; animal tissue; cell survival; cancer immunotherapy; cell line; animal model; stem cell transplantation; antineoplastic activity; cell line, tumor; transfection; oncology; immunology; genetic engineering; cell culture; irradiation; graft versus host reaction; biocompatibility; major histocompatibility complex; immunotherapy, adoptive; cd19 antigen; notch1 receptor; tumor immunotherapy; lymphoid cell; chimeric receptors; major histocompatibility complex (mhc); precursor cells, t-lymphoid
Journal Title: Nature Biotechnology
Volume: 26
Issue: 4
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2008-04-01
Start Page: 453
End Page: 461
Language: English
DOI: 10.1038/nbt1395
PUBMED: 18376399
PROVIDER: scopus
PMCID: PMC2731996
DOI/URL:
Notes: --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: NABIF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Glenn Heller
    303 Heller
  2. Renier J Brentjens
    195 Brentjens
  3. Robert R Jenq
    102 Jenq
  4. Michel W J Sadelain
    456 Sadelain
  5. Isabelle C Riviere
    164 Riviere
  6. Christopher King
    29 King
  7. Sydney X Lu
    51 Lu
  8. Odette Marsinay Smith
    95 Smith
  9. David Suh
    41 Suh
  10. Amanda M Holland
    52 Holland
  11. Gabrielle A Rizzuto
    21 Rizzuto
  12. Jeremy Grubin
    10 Grubin