1、T 细胞免疫疗法治疗白血病齐鲁细胞刘兆云译近 90%的儿童、成人极易患急性淋巴细胞白血病（ALL） ，但至今扔没有证据表明个体化细胞治疗能重建患者的免疫系统功能。生物工程改造的 T 细胞杀伤白血病细胞的初步研究发现，经这种 T 细胞治疗 28 天后 27 名白血病患者（22 名在费城儿童医院接受治疗的儿童以及 5 名在宾夕法尼亚大学医院接受治疗的病人）中有 24 名患者病情完全缓解。费城儿童医院儿科教授、儿科肿瘤学家；宾夕法尼亚大学佩雷尔曼医学院的教授Stephan A，Grupp 在新奥尔良举办的美国血液学学会年会中首次公布这一结果。Stephan A，Grupp 教授说： “ 我们的这一研
2、究结果为那些没有其它治疗选择的患者进行细胞治疗提供了另外一种可能。而且这一方法对那些接受骨髓移植后复发的患者是安全有效的。 ”所有在初步治疗后复发以及在一开始就拒绝治疗的所有高风险患者均接受一种被叫做CTL019 T 细胞治疗。第一个接受这种治疗的是一个叫 Emily 的 8 岁孩子，她从 2012 年4 月第一次接受这种治疗后至今仍保持无复发生存状态，并且还能上学、陪狗狗玩及所有儿童能进行的其它活动。在接受治疗 2.6 个月后的评估中发现在完全缓解的 24 名患者中又有 6 名发生了转移，也就是只有 18 名患者完全缓解。这一实验是由费城儿童医院以及宾夕法尼亚大学合作并在医学博士，病理研究中
3、心免疫疗法教授、癌症研究中心医学转化主任 Carl H. June 的指导下完成。 这是治疗癌症的一种新策略，这种免疫疗法依赖于 T 细胞重新恢复机体的免疫系统，因为 B 细胞在 ALL 白血病中已经癌变，CTL019 像是肿瘤猎人，捕杀逃离正常 T 细胞监视的白血病细胞。研究人员提取患者自体 T 细胞并在 Penns 细胞及疫苗作用下通过基因改造创建 CTL019 细胞。生物工程技术是将病人的 T 细胞表面嵌合上抗原受体识别只表达在 B 细胞表面的 CD19 蛋白分子，然后将这些细胞回输到病人体内增殖并且清除 B 细胞，不仅如此它们存在于血液循环中发挥防止肿瘤复发的作用。尽管大多数成人 AL
4、L 对药物治疗有效，但将近半数的病人会发生转移，使得本病的完全治愈率仅在 40%左右。一旦病人发生转移，治疗往往是无效的，不仅如此这些病人也没有了骨髓移植的机会，因此这种方法给了他们一个在没有选择情况下的一个选择。因为 CTL090 细胞不仅有潜在的杀伤肿瘤细胞的作用还能刺激引起有毒的免疫反应即：细胞因子释放综合征。本研究团队应用两种免疫调节药物成功的抑制了这一副作用。另外，CTL090 治疗不仅能杀死生癌 B 淋巴细胞还能清除正常的 B 淋巴细胞，所以病人必须接受免疫球蛋白重建由正常 B 细胞提供的免疫功能。Grupp 说， “ALL 实验证明这种经基因改造的细胞能很大程度上延长病人的生存期
5、限，提高完全缓解率，并且在病人体内持续存在，使疾病能得到长期控制。我们期望能在接下来的儿童及成人试验中能检测到这种细胞。 ”T cell immunotherapy shows promising results in children, adults with leukemiaNearly 90 percent of children and adults with a highly aggressive form of acute lymphoblastic leukemia (ALL) showed no evidence of cancer after receiving a nove
6、l, personalized cell therapy that reprograms a patients immune system. In pilot studies of bioengineered T cells that attack leukemia, 24 of 27 patients (89%) experienced complete responses within 28 days after treatment. In all, 27 patients received the treatment-22 children treated at The Children
7、s Hospital of Philadelphia and five adults treated at the Hospital of the University of Pennsylvania.Pediatric oncologist Stephan A. Grupp, M.D., Ph.D., of The Childrens Hospital of Philadelphia and a Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania, prese
8、nted outcomes and follow-up results of this immunotherapy clinical trial for pediatric and adult patients with ALL in a press program today at the annual meeting of the American Society of Hematology (ASH) in New Orleans.“Our results serve as another important milestone in demonstrating the potentia
9、l of this cell therapy for patients who have no other therapeutic options,“ said study author Grupp. “We are also very excited that this approach has worked and been safe in patients who have relapsed after a bone marrow transplant.“All the patients had high-risk ALL that recurred after initial trea
10、tment or resisted that treatment from the start. Patients received bioengineered “hunter“ T cells called CTL019 cells.The first child to undergo this therapy, 8-year-old Emily Whitehead, remains cancer-free since her T cell treatment in April 2012, and has gone on to enjoy typical childhood activiti
11、es like going to school and playing with her dog, Lucy. Emily has appeared prominently in news articles since her doctors announced dramatic findings during the December 2012 ASH meeting.In follow-up assessments, the researchers reported six relapses among the 24 patients with complete responses. Th
12、erefore, 18 of the 24 pediatric and adult patients had ongoing complete responses at a median follow-up of 2.6 months after treatment.The trials, a collaboration between The Childrens Hospital of Philadelphia and the University of Pennsylvania, are overseen by Carl H. June, M.D., the Richard W. Vagu
13、e Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penns Abramson Cancer Center.A relatively new approach in cancer treatment, this type of immunotherapy relies on T cells, the workhorses of the bodys immune system. Because B
14、 cells become cancerous in specific leukemias such as ALL, CTL019 cells function as cancer hunters, killing the leukemia cells that normally evade regular T cell surveillance. Researchers first extract a patients own T cells and genetically modify them in Penns cell and vaccine production facility t
15、o create CTL019 cells. Bioengineering techniques are used to reprogram each patients T cells into chimeric antigen receptor cells - the CTL019 cells - custom-designed to bind to a protein called CD19 that exists only on the surface of B cells. Then, the cells are returned to the patients body, where
16、 they proliferate and then eliminate B cells. Moreover, they persist in the circulation, helping to guard against the cancers recurrence.“Although most adults with ALL respond to drug treatment, as many as half of them eventually relapse, putting the overall cure rate for the disease only around 40
17、percent,“ said David L. Porter, M.D., a professor of Medicine and director of Blood and Marrow Transplantation in Penns Abramson Cancer Center, who leads the adult CLL and ALL trials along with Noelle Frey, M.D., an assistant professor of Medicine. “Once a patient relapses, treatments are often inef
18、fective. Many of these patients are not even eligible for bone marrow transplants, so this approach stands to give them an option where they would otherwise have had none.“As the CTL019 cells potently attacked leukemia cells, they also stimulated an unwanted, toxic immune response called cytokine re
19、lease syndrome. The care team successfully counteracted these side effects with two immunomodulating drugs. In addition, because the CTL019 therapy eliminates healthy B cells along with cancerous B cells, patients must receive infusions of immunoglobin to perform the immune function provided by norm
20、al B cells.“The results from the ALL and CLL trials also demonstrate that these engineered hunter cells greatly expand in patients, producing very high complete response rates, and then persist in patients, potentially allowing for long-term disease control. We are looking forward to testing these cells in upcoming multicenter pediatric and adult trials,“ said Grupp.（本文由齐鲁细胞刘兆云翻译）
