Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens
Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens
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DOI：
10.1182/blood-2009-10-248997
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发表时间：
2010-05-13
期刊：
影响因子：
20.3
通讯作者：
Riddell, Stanley R.
中科院分区：
文献类型：
--
作者：
Warren, Edus H.;Fujii, Nobuharu;Riddell, Stanley R.
识别受体次要组织相容性抗原（mHAgs）的供体T细胞的过继转移是预防或治疗同种异体造血细胞移植（HCT）后白血病复发的潜在策略。共7例主要组织相容性复合体（MHC）匹配异体HCT后复发性白血病患者接受输注供体来源的体外扩增CD8（+）细胞毒性T淋巴细胞（CTL）克隆，特异性用于组织限制性受体mHAgs。评估了t细胞治疗的安全性、转移的ctl的体内持久性和疾病反应。对3例患者的CTL克隆识别的mHAgs进行了分子表征，以深入了解t细胞治疗的抗白血病活性和安全性。CTL输注3例出现肺毒性，1例出现重度肺毒性，与肺组织中mhag编码基因的表达水平相关。过继性转移的ctl在输注后可在血液中持续21天，5例患者在治疗后获得了完全但短暂的缓解。这些研究的结果说明了通过过继转移mhag特异性t细胞克隆选择性地增强移植物抗白血病活性的潜力，以及该方法在同种异体HCT中广泛应用的挑战。本研究已在http://clinicaltrials.gov注册，编号为NCT00107354。[血液。2010;115(19):3869-3878]
The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC) matched allogeneic HCT were treated with infusions of donor-derived, ex vivo expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graftversus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354. (Blood. 2010; 115(19): 3869-3878)