Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation
Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation
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DOI：
10.1111/j.1537-2995.2010.02940.x
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发表时间：
2011-03-01
期刊：
影响因子：
2.9
通讯作者：
Schmitt, Michael
中科院分区：
文献类型：
--
作者：
Schmitt, Anita;Tonn, Torsten;Schmitt, Michael
背景：巨细胞病毒（CMV）疾病是同种异体干细胞移植后的严重并发症。对于CMV的清除，CD8+ T细胞是关键。研究设计和方法：在本研究中，新型链载体技术在GMP水平下用于将CMV特异性T细胞过继转移到异基因干细胞移植后复发性高CMV抗原血症的急性白血病患者中。结果：单次输血后，cmv特异性CD8+CD45RA+CCR7-效应T细胞占所有T细胞的比例从0.0%急剧增加到27.1%。这些T细胞显然是来源于供体，而不是源于内在重构，这可以通过分析1)通过单串联重复序列的供体嵌合，2)T细胞受体切除环，以及3)通过聚合酶链反应的V β链分型来证明。在临床上，特异性t细胞转移导致CMV抗原血症的持续清除，这使得患者可以停止毒性抗病毒药物治疗，而不会进一步高水平地重新激活CMV，这证明了链tamer技术的力量。结论：综上所述，streptamer技术具有在GMP水平上选择病毒特异性CD8+ T细胞进行过继性T细胞转移的优势，从而诱导持久的特异性CD8+ T细胞反应，而不会增加移植物抗宿主病的风险。
BACKGROUND: Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic stem cell transplantation. For the clearance of CMV, CD8+ T cells are pivotal.STUDY DESIGN AND METHODS: Here, the novel streptamer technology was used at good manufacturing practice (GMP) level for adoptive transfer of CMV-specific T cells into acute leukemia patients with recurrent high CMV antigenemia after allogeneic stem cell transplantation.RESULTS: After a single transfusion, the frequency of CMV-specific CD8+CD45RA+CCR7- effector T cells increased dramatically from 0.0% to a maximum of 27.1% of all T cells. These T cells were clearly donor derived and did not stem from intrinsic reconstitution, as demonstrated by analysis of 1) donor chimerism through single-tandem repeats, 2) T-cell receptor excision circles, and 3) V beta-chain typing by polymerase chain reaction. Clinically, the specific T-cell transfer resulted in a persistent clearance of the CMV antigenemia, which allowed the patients to discontinue toxic antiviral drug therapy without further high-level reactivation of CMV, demonstrating the power of the streptamer technology.CONCLUSION: Taken together, the streptamer technology offers the advantage of selecting virus-specific CD8+ T cells at GMP level for adoptive T-cell transfer, thus inducing long-lasting specific CD8+ T-cell responses without increasing the risk for graft-versus-host disease.