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摘要
“无实质性植入同种异体细胞治疗”(ACT-WiSE)是指自然过继转移(“非工程”)人类白细胞抗原不相合淋巴细胞介导受体的抗肿瘤免疫抑制同种异体反应性不使用药物。根据定义,无实质性植入同种异体细胞治疗需要随后大多排斥反应,如果不是全部,供体细胞。嵌合体是短暂的和微嵌合体可以是短暂的存活或持续的。该策略利用同种异体反应性的抗癌效力不产生显着的移植物抗宿主病的风险。”微移植”指的是无实质性植入同种异体细胞治疗的一种形式,在供体细胞产品含有造血祖细胞。因此,微移植促进造血恢复其免疫调节作用可能不同于其他形式的无实质性植入同种异体细胞治疗。最近的研究表明,各种形式的无实质性植入同种异体细胞治疗,包括微移植,可以提高在骨髓恶性肿瘤患者化疗敏感性,从而导致更高的完全缓解率和生存率的提高。微移植试验结果也显示出可喜的难治性或复发性非霍奇金淋巴瘤和霍奇金淋巴瘤。无实质性植入同种异体细胞治疗和微移植可以建立一类新的特别相关的异体细胞疗法的人不考虑传统的异基因造血干细胞移植(AHCT)候选人。开放式问题的最佳时机和明智的行为细胞剂量,其中供体因素有助于疗效,以及是否这些缓解持久的供体细胞根除后。我们将在传统和半相合AHCT提出明智的行为方式优化过程的经验教训。我们把这些捐赠的相关策略(包括合理的供选择和提高NK细胞和T细胞同种异体反应性)和病人相关的策略(这可能有利于自体NK细胞和T细胞介导的发展后采取无实质性植入同种异体细胞治疗的窗口抗癌细胞毒性)。
关键词: 同种异体反应性,移植物抗宿主病,免疫治疗,白血病,自然杀伤细胞,T细胞,移植,肿瘤相关抗原
Current Drug Targets
Title:Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers
Volume: 18 Issue: 3
Author(s): Elizabeth F. Krakow, Hui-Sheng Ai, Brian Shaffer, Jean-Sebastien Delisle, Kai-Xun Hu, Anthony D. Sung.
Affiliation:
关键词: 同种异体反应性,移植物抗宿主病,免疫治疗,白血病,自然杀伤细胞,T细胞,移植,肿瘤相关抗原
摘要: "Alloreactive cell therapy without substantial engraftment" (ACT-WiSE) refers to adoptive transfer of natural (“non-engineered”) human leukocyte antigen-mismatched lymphocytes to mediate anti-neoplastic alloreactivity in recipients without employing pharmacologic immunosuppression. By definition, ACT-WiSE entails subsequent rejection of most, if not all, donor cells. Macrochimerism is transient and microchimerism may be either short-lived or persistent. This strategy harnesses the anticancer potency of alloreactivity without incurring significant risk of graft-versus-host disease. "Microtransplantation" refers to a form of ACT-WiSE where the donor cell product contains hematopoietic progenitor cells. Microtransplantation therefore accelerates hematopoietic recovery and its immunomodulatory effects may differ from other forms of ACT-WiSE. Recent studies suggest that various forms of ACT-WiSE, including microtransplantation, may improve chemosensitivity in patients with myeloid malignancies, resulting in higher complete remission rates and increased survival. Microtransplantation has also demonstrated promising pilot results in relapsed or refractory Non-Hodgkin and Hodgkin lymphoma. ACT-WiSE and microtransplantation may establish a new class of allogeneic cell therapy of particular relevance to persons not considered candidates for traditional allogeneic hematopoietic cell transplantation (AHCT). Open questions include the optimal timing and cell dose of ACT-WiSE, which donor factors contribute to efficacy, and whether these remissions are durable after eradication of donor cells. We extrapolate from lessons learned in the course of traditional and haploidentical AHCT to propose ways of optimizing ACT-WiSE. We divide these into donor-related strategies (including rational donor selection and boosting NK-cell and T-cell alloreactivity) and patient- related strategies (that may favor development of autologous NK-cell and T-cell mediated anticancer cytotoxicity in the post-ACT-WiSE window).
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Elizabeth F. Krakow, Hui-Sheng Ai, Brian Shaffer, Jean-Sebastien Delisle, Kai-Xun Hu, Anthony D. Sung. , Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers, Current Drug Targets 2017; 18 (3) . https://dx.doi.org/10.2174/1389450116666150304103849
DOI https://dx.doi.org/10.2174/1389450116666150304103849 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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