Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.
Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.
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DOI：
10.1016/j.bbmt.2014.11.001
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Korngold R
中科院分区：
文献类型：
--
作者：
Zilberberg J;Feinman R;Korngold R
异基因血液和骨髓移植(allo-BMT)是一种有效的免疫治疗方法，可为恶性血液病患者提供部分或完全缓解。供体接种中的成熟供体T细胞在介导移植物抗肿瘤(GVT)反应中发挥核心作用，它通过破坏保留在条件化方案后的肿瘤细胞。对次要组织相容性抗原(MIHA)的同种异体反应性是GVT发生的主要因素。次要组织相容性抗原是受体细胞上主要组织相容性复合体(MHC)分子背景下的各种组织相关自肽，其中一些可能存在于肿瘤细胞上。潜在地，GVT也可以针对肿瘤相关抗原或肿瘤特异性抗原，这些抗原对肿瘤细胞本身更具特异性。然而，移植物抗宿主病(GVHD)的发展极大地限制了allo-BMT的充分利用，移植物抗宿主病(GVHD)是由供体T细胞对受体肠道、皮肤和肝脏细胞中表达的MiHA的反应介导的。由于移植物抗宿主病(GVT)和移植物抗宿主病(GVHD)反应在决定患者临床预后方面的重要性，MIHA和肿瘤抗原已被广泛研究，而分离这两种反应的一种积极的免疫治疗方法是异基因骨髓移植后的肿瘤疫苗接种。这两种策略的结合比没有allo-BMT的患者接种疫苗更有优势，因为他或她的免疫系统已经暴露，对肿瘤抗原没有反应。Allo-BMT的调节消除了患者现有的免疫系统，包括调节元件，并为新开发的供体免疫隔间提供了一个更宽松的环境，以选择性地靶向恶性细胞。利用最近的技术进步，许多人MIHA和肿瘤抗原肽的身份已经确定，目前正在临床和基础免疫学研究中评估它们产生有效T细胞反应的能力。迈向这一目标的第一步是识别靶向肿瘤抗原。在这篇综述中，我们将重点介绍目前在血液系统恶性肿瘤中用于识别肿瘤抗原和抗肿瘤T细胞克隆的一些技术。
Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies.
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DOI：
10.4049/jimmunol.1201641
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fanning SL;Zilberberg J;Stein J;Vazzana K;Berger SA;Korngold R;Friedman TM
通讯作者：
Friedman TM
影响因子：
32.4
作者：
BOEL, P;WILDMANN, C;VANDERBRUGGEN, P
通讯作者：
VANDERBRUGGEN, P
影响因子：
4.3
作者：
Alyea, Edwin P.;DeAngelo, Daniel J.;Moldrem, Jeffrey;Pagel, John M.;Przepiorka, Donna;Sadelin, Michel;Young, James W.;Giralt, Sergio;Bishop, Michael;Riddell, Stan
通讯作者：
Riddell, Stan
DOI：
10.1007/s00262-011-1009-3
发表时间：
2011-07
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Anderson LD Jr;Cook DR;Yamamoto TN;Berger C;Maloney DG;Riddell SR
通讯作者：
Riddell SR
影响因子：
2.2
作者：
Feldhahn, Magdalena;Doennes, Pierre;Kohlbacher, Oliver
通讯作者：
Kohlbacher, Oliver