CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD30+ Lymphoproliferative Disorders as Potential Candidates for CD30-Targeted Therapies.
CD30+ Lymphoproliferative Disorders as Potential Candidates for CD30-Targeted Therapies.
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背景。——在20世纪80年代初,针对一株来源于霍奇金淋巴瘤患者的细胞系,研制了一种称为Ki-1的单克隆抗体。该抗体在淋巴组织中仅检测到少量良性活化淋巴细胞,而在霍奇金淋巴瘤中,它似乎对Reed-Sternberg细胞及其单核变异型几乎具有特异性。随后的研究表明,Ki-1表达定义了一种新型淋巴瘤,后来被命名为间变性大细胞淋巴瘤,伴或不伴间变性大细胞激酶表达/易位。在过去30年中,已定义了众多新的淋巴瘤类型,其中许多对CD30呈不同程度的阳性。许多病毒转化的淋巴增殖性疾病也常常对CD30呈阳性。目的。——阐述CD30+血液系统恶性肿瘤的广泛谱系,并提供CD30靶向治疗的最新进展。数据来源。——个人经验及PubMed中已发表的研究。结论。——由于CD30在正常组织中低表达,多年来一直被研究作为治疗靶点。
然而,首个功能性抗CD30人源化抗体仅在大约10年前才被研制出来。Brentuximab vedotin是一种人源化抗CD30抗体与细胞毒素偶联物,于2012年被美国食品药品监督管理局批准用于治疗难治性霍奇金淋巴瘤和间变性大细胞淋巴瘤。自那时起,美国食品药品监督管理局批准的CD30靶向血液系统恶性肿瘤的名单不断增加。近年来,使用靶向CD30的肿瘤抗原特异性CAR-T 细胞疗法引起了极大热情,并正在临床试验中进行研究。
CONTEXT. —: In the early 1980s, a monoclonal antibody termed Ki-1 was developed against a cell line derived from a patient with Hodgkin lymphoma. This antibody detected a limited number of benign activated lymphocytes in lymphoid tissue, whereas in Hodgkin lymphoma it appeared to be nearly specific for Reed-Sternberg cells and their mononuclear variants. Subsequent studies showed that Ki-1 expression defined a new type of lymphoma that was later designated anaplastic large cell lymphoma with or without anaplastic large cell kinase expression/translocation.
In the past 30 years, numerous new lymphoma entities have been defined, many of which are variably positive for CD30. Many virally transformed lymphoproliferative disorders are also frequently positive for CD30. OBJECTIVE. —: To illustrate the broad spectrum of CD30+ hematologic malignancies and to provide an update of CD30-targeted therapies. DATA SOURCES. —: Personal experiences and published works in PubMed. CONCLUSIONS. —: Because of its low expression in normal tissue, CD30 was studied as a therapeutic target for many years.
However, the first functional humanized antibody against CD30 was developed only about 10 years ago. Brentuximab vedotin is a humanized anti-CD30 antibody linked to a cytotoxin, and was approved by the US Food and Drug Administration in 2012 for treating refractory Hodgkin lymphoma and anaplastic large cell lymphoma.
Since then, the list of Food and Drug Administration-approved CD30-targeted hematologic malignancies has grown. Recently, the therapies using tumor antigen-specific chimeric antigen receptor T cells targeting CD30 have incited a great deal of enthusiasm and are studied in clinical trials.
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