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
Citation Impact
MSK Authors
Related MSK Work