Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Haematologica. 2012 Nov;97(11):1622-31. doi: 10.3324/haematol.2012.064303. Epub 2012 Aug 28.
Modern chemotherapy regimens and supportive care have produced remarkable improvements in the overall survival of patients with hematologic malignancies. However, the development of targeted small molecules, monoclonal antibodies, and biological therapies that demonstrate greater efficacy and lower toxicity remains highly desirable in hematology, and oncology in general. In the context of biological therapies, T-lymphocyte based treatments have enormous potential. Donor lymphocyte infusion in patients relapsed after allogeneic hematopoietic stem cell transplant pioneered the concept that T lymphocytes can effectively control tumor growth, and this was then followed by the development of cell culture strategies to generate T lymphocytes with selective activity against tumor cells. Over the past decade, it has become clear that the adoptive transfer of ex vivo expanded antigen-specific cytotoxic T lymphocytes promotes sustained antitumor effects in patients with virus-associated lymphomas, such as Epstein-Barr virus related post-transplant lymphomas and Hodgkin's lymphomas. Because of this compelling clinical evidence and the concomitant development of methodologies for robust gene transfer to human T lymphocytes, the field has rapidly evolved, offering new opportunities to extend T-cell based therapies. This review summarizes the most recent biological and clinical developments using genetically manipulated T cells for the treatment of hematologic malignancies.
现代化疗方案和支持性护理使血液系统恶性肿瘤患者的总体生存率得到了显著提高。然而，在血液学和肿瘤学领域，仍非常需要开发具有更高疗效和更低毒性的靶向小分子、单克隆抗体和生物疗法。在生物疗法方面，基于 T 淋巴细胞的治疗具有巨大的潜力。在异基因造血干细胞移植后复发的患者中输注供体淋巴细胞开创了 T 淋巴细胞可以有效控制肿瘤生长的概念，随后开发了细胞培养策略来产生对肿瘤细胞具有选择性活性的 T 淋巴细胞。在过去的十年中，已经清楚地表明，体外扩增的抗原特异性细胞毒性 T 淋巴细胞的过继转移可促进病毒相关性淋巴瘤（如 EBV 相关移植后淋巴瘤和霍奇金淋巴瘤）患者的持续抗肿瘤作用。由于这一引人注目的临床证据以及对人类 T 淋巴细胞进行强大基因转移的方法学的同时发展，该领域迅速发展，为扩展基于 T 细胞的治疗提供了新的机会。这篇综述总结了使用基因修饰的 T 细胞治疗血液系统恶性肿瘤的最新生物学和临床进展。
