Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

被引：97

作者：

Zakrzewski, Johannes L. ^{[1
]}

Suh, David ^{[1
]}

Markley, John C. ^{[2
]}

Smith, Odette M. ^{[1
]}

King, Christopher ^{[1
]}

Goldberg, Gabrielle L. ^{[1
]}

Jenq, Robert ^{[1
,3
]}

Holland, Amanda M. ^{[1
]}

Grubin, Jeremy ^{[1
]}

Cabrera-Perez, Javier ^{[1
]}

Brentjens, Renier J. ^{[3
]}

Lu, Sydney X. ^{[1
]}

Rizzuto, Gabrielle ^{[1
]}

Sant'Angelo, Derek B. ^{[1
]}

Riviere, Isabelle ^{[2
]}

Sadelain, Michel ^{[2
,3
]}

Heller, Glenn ^{[4
]}

Zuniga-Pflucker, Juan Carlos ^{[5
]}

Lu, Chen ^{[6
]}

van den Brink, Marcel R. M. ^{[1
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[5] Univ Toronto, Sunnybrook Res Inst, Dept Immunol, Toronto, ON M4N 3M5, Canada

[6] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

来源：

NATURE BIOTECHNOLOGY | 2008年 / 26卷 / 04期

关键词：

D O I：

10.1038/nbt1395

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：453 / 461

页数：9

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