Ohmine Ken
Division of Hematology, Department of Medicine, Jichi Medical University.
Division of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University.
Rinsho Ketsueki. 2018;59(8):1058-1065. doi: 10.11406/rinketsu.59.1058.
A chimeric antigen receptor (CAR) comprises an extracellular ligand recognition domain linked to CD3ζ and induces T-cell activation upon antigen binding. Recently, the potential of CD19-targeted CAR T-cells (CAR-T) to treat multiple myeloma has been explored. A group in the University of Pennsylvania reported that 4 out of 10 patients with refractory myeloma achieved an objective response (sCR: 1, VGPR: 1, and PR: 2). Although the resultant cancer ablation was an arresting sight, it remains unclear whether CD19 is a suitable target for myeloma. Therefore, CAR-T therapy employing alternative target antigens is being attempted. Some current clinical trials are utilizing CAR against differentiation antigens, including CD138, CD38, and kappa light chain. B-cell maturation antigen (BCMA) is also a potential candidate. A group in the NCI described 12 patients with refractory myeloma enrolled in a BCMA-CAR phase 1 clinical trial. Two patients receiving the highest dosage attained an objective response. Nevertheless, considerable research is required for CAR immunotherapy to become universally available to patients with myeloma. The current enthusiasm for the development of this cutting-edge technology is justified because extraordinary evidence indicates that it is effective, although this may not apply to every case. CAR-T therapy for myeloma is currently undergoing rapid, wide-scale growth both in academia and in industry-sponsored clinical development.
嵌合抗原受体(CAR)由与CD3ζ相连的细胞外配体识别结构域组成,并在抗原结合后诱导T细胞活化。最近,已对靶向CD19的嵌合抗原受体T细胞(CAR-T)治疗多发性骨髓瘤的潜力进行了探索。宾夕法尼亚大学的一个研究小组报告称,10例难治性骨髓瘤患者中有4例获得了客观缓解(严格完全缓解:1例,非常好的部分缓解:1例,部分缓解:2例)。尽管由此产生的癌症消融是一个惊人的景象,但CD19是否是骨髓瘤的合适靶点仍不清楚。因此,正在尝试采用替代靶抗原的CAR-T疗法。目前的一些临床试验正在利用针对分化抗原的CAR,包括CD138、CD38和κ轻链。B细胞成熟抗原(BCMA)也是一个潜在的候选靶点。美国国立癌症研究所的一个研究小组描述了12例参加BCMA-CAR 1期临床试验的难治性骨髓瘤患者。两名接受最高剂量治疗的患者获得了客观缓解。然而,CAR免疫疗法要想普遍应用于骨髓瘤患者,还需要进行大量研究。目前对这项前沿技术发展的热情是合理的,因为有大量证据表明它是有效的,尽管这可能并不适用于每一个病例。目前,骨髓瘤的CAR-T疗法在学术界和行业赞助的临床开发中都在迅速、广泛地发展。