Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia.

Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia.
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DOI:
10.1038/icb.2010.124
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发表时间:
2011-03
影响因子:
4
通讯作者:
Riddell, Stanley R.
Riddell, Stanley R.
中科院分区:
医学3区
文献类型:
--
作者:
Bleakley, Marie;Riddell, Stanley R.

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次要组织相容性(H)抗原是人类白细胞抗原相同个体之间同种异体造血细胞移植(HCT)后供体CD8+和CD4+T细胞介导的移植物抗白血病(GVL)效应的主要靶点。在人类次要H抗原的第一个分子表征以来的15年中,由于细胞、遗传和分子技术的进步,次要H抗原的发现取得了重大进展。关于次要H抗原免疫原性的机制,它们在正常和恶性细胞上的表达,以及它们在GVL应答中的作用,已经了解了很多。对白血病细胞(包括白血病干细胞)上表达的次要H抗原具有特异性的T细胞可以在体外分离和扩增,并输注到同种异体HCT受体中以增强GVL效应,从而预防和治疗复发。2010年首次报告了将次要H抗原特异性T细胞克隆过继转移给白血病复发患者,说明了操纵同种异体反应性以获得治疗益处的潜力。本文综述了T细胞识别人类次要H抗原的最新进展,以及将这些发现转化为减少异基因HCT后白血病复发的努力。
Minor histocompatibility (H) antigens are major targets of a graft‐versus‐leukemia (GVL) effect mediated by donor CD8+and CD4+T cells following allogeneic hematopoietic cell transplantation (HCT) between human leukocyte antigen identical individuals. In the 15 years since the first molecular characterization of human minor H antigens, significant strides in minor H antigen discovery have been made as a consequence of advances in cellular, genetic and molecular techniques. Much has been learned about the mechanisms of minor H antigen immunogenicity, their expression on normal and malignant cells, and their role in GVL responses. T cells specific for minor H antigens expressed on leukemic cells, including leukemic stem cells, can be isolated and expandedin vitroand infused into allogeneic HCT recipients to augment the GVL effect to prevent and treat relapse. The first report of the adoptive transfer of minor H antigen‐specific T‐cell clones to patients with leukemic relapse in 2010 illustrates the potential for the manipulation of alloreactivity for therapeutic benefit. This review describes the recent developments in T‐cell recognition of human minor H antigens, and efforts to translate these discoveries to reduce leukemia relapse after allogeneic HCT.
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