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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：“ 我们的这一研究结果为那些没有其它治疗选择的
2、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，病理研究中心免疫疗法教授、癌症研究中心医学转化主任Carl H. Ju
3、ne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ALL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
4、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 cel
5、l 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 novel, personalized cell therapy that reprograms a patients immune syst
6、em. 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 Childrens Hospital of Philadelphia and five adults treated at the Hospital
7、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, presented outcomes and follow-up results of this immunotherapy clinical
8、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 potential of this cell therapy for patients who have no other therapeutic op
9、tions, 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 treatment or resisted that treatment from the start. Patients received bioe
10、ngineered 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 activities like going to school and playing with her dog, Lucy. Emily has appeare
11、d 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. Therefore, 18 of the 24 pediatric and adult patients had ongoing complete r
12、esponses 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. Vague Professor in Immunotherapy in the department of Pathology and Laborator
13、y 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 cells become cancerous in specific leukemias such as ALL, CTL019 cells f
14、unction 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 to create CTL019 cells. Bioengineering techniques are used to reprogram ea
15、ch 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 they proliferate and then eliminate B cells. Moreover, they persist in t
16、he 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 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
