Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors
Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors
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DOI：
10.1038/nbt1395
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发表时间：
2008-04-01
影响因子：
46.9
通讯作者：
van den Brink, Marcel R. M.
中科院分区：
文献类型：
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作者：
Zakrzewski, Johannes L.;Suh, David;van den Brink, Marcel R. M.
我们提出了一种使用Notch1培养产生的T系致力于淋巴前体细胞的过继免疫治疗的策略。我们发现，无论主要组织相容性复合体(MHC)的差异如何，同种异体T细胞前体都可以转移到受照射的个体，并产生宿主MHC限制性和宿主耐受的同种异体T细胞，提高受者的存活率，同时增强抗肿瘤反应。T细胞前体细胞被转导表达针对hCD19的嵌合受体，导致显著的额外的抗肿瘤活性，证明了这些细胞基因工程的可行性。我们的结论是，来自任何捐赠者的体外产生的MHC不同的T细胞前体可以普遍用于现成的免疫治疗，并可以通过基因工程进一步增强靶向免疫治疗。
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.