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

Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.

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1
Department Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.

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.

PMID:
18376399
PMCID:
PMC2731996
DOI:
10.1038/nbt1395
[Indexed for MEDLINE]
Free PMC Article

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