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靶向CD19的CAR-T细胞对抗恶性血液病

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发表于 2015-12-7 22:24:46 | 显示全部楼层 |阅读模式
  CD19-Targeted T Cells for Hematologic Malignancies  
Abstract:
Recently, immunotherapy for cancer has begun to garner traction with encouraging results in a number of malignancies. Included within this arena has been the genetic engineering of autologous T cells with chimeric antigen receptors (CARs) against tumor target. The majority of this experience has included the use of CAR T cells directed against CD19 for B-cell hematologic malignancies. The most striking efficacy to date with CAR T cells directed against CD19 has been in relapsed and refractory B-cell acute lymphoblastic leukemia, with the overwhelming majority of patients experiencing complete remissions. In addition, singlecenter and largely early-phase studies have demonstrated responses in patients with varying histologic findings of relapsed and refractory B-cell non-Hodgkin lymphoma. The favorable response rates seen with this technology have been tempered by the high risk of toxicity, particularly in the form of cytokine-release syndrome and neurotoxicity. Agents such as tocilizumab and corticosteroids have been used to treat these toxicities. The current state of the science includes strategies to circumvent and treat toxicity, manufacturing, and study of later-generation CAR constructs with the intention of improving efficacy and development of CARs against other tumor targets for both hematologic and solid tumor malignancies. The observation of an early efficacy ensures further integration and development of this modality into future immunotherapeutic strategies for various cancers.
Key Words: Cancer, chimeric antigen receptor, immunotherapy
靶向CD19CAR-T细胞对抗恶性血液病
摘要:
最近,免疫肿瘤疗法在一些恶性肿瘤的治疗中获得了令人鼓舞的成果,从而使得该疗法加大了发展速度。在这个领域,包括了使用基因改造的自体嵌合抗原修饰的T细胞对抗肿瘤靶点。这个试验主要包括了使用CAR-T细胞靶向CD19来对抗B淋巴细胞恶性血液疾病。到目前为止,最引人注意的是靶向CD19的嵌合抗原受体修饰的CAR-T细胞对抗复发性/难治性急性淋巴细胞白血病,对绝大多数病人有完全的缓解作用。此外,单中心和大量的早期研究已经说明对于不同组织学表型的复发性/难治性B细胞非霍奇金淋巴瘤都有效果。这种治疗方法有良好的反应有效性,但是会有高风险的毒副反应,特别是细胞因子释放综合症和神经毒性。使用一些药物、糖皮质激素已被用于治疗这些毒性。目前这门学科主要集中在缓解和治疗毒性、生产和最新代CAR结构组成等领域,关注于增加CAR-T对抗血液和实体肿瘤的其他靶点的疗效和发展。一个早期有效性的观察能够确保这种方式进一步的整合和发展,在将来能够对各种不同的癌症进行免疫治疗。
关键词:肿瘤,嵌合抗原受体,免疫治疗
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CD19-Targeted T Cells for Hematologic Malignancies 2015.12.7.pdf

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