Chimeric antigen receptor T-cells for B-cell malignancies

Abstract

The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern. There continues to be substantial heterogeneity among CAR-T products, and differences in both CAR designs and CAR-T production strategies can substantially affect clinical outcomes. Ongoing clinical studies will further elucidate these differences and many other innovative approaches are being evaluated at the preclinical level. In this review, we will discuss the background and rationale for the use of CAR-Ts, provide an overview of advances in the field, and examine the application of CAR-Ts to the treatment of B-cell malignancies, including a summary of clinical trials published to date.

The Significance of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Human Gliomas

“…It is expressed on the surface of tumor cells and vascular pericytes, besides a relatively restricted distribution in healthy tissues to be proposed as an attractive candidate to target, simultaneously, both the malignant and stromal cell compartments within the tumor [ 26 ]. Based on its structure, distribution, and functions, NG2/CSPG4 has been suggested to promote tumor progression by multiple mechanisms and represents, to date, a powerful target for chimeric antigen receptor-based T-cell (CAR-T) immunotherapy of solid and hematological malignancies [ 27 , 28 , 29 ].…”

Sequential allogeneic and autologous CAR-T–cell therapy to treat an immune-compromised leukemic patient

“…[1][2][3] Successes for treating B-cell acute lymphoblastic leukemia (B-ALL) with CD19 CAR-T cells range from 67% to 90% in multiple clinical trials. [4][5][6] We have developed a new generation of CAR-T-cell technology based on CD28 and CD27 T-cell costimulatory signals and included an inducible caspase 9 suicide gene design.…”

Recent advances in immunotherapy of acute leukemia via chimeric antigen receptor-engineered T cells

“…试验 [68] . 在不同诊疗中心, 不同国家, 使用不同结构 的CAR-T细胞类型、淋巴细胞清除方案、自体或异 体T细胞以及不同的CAR-T回输数量治疗难治复发的 B-ALL患者, 其中50%~90%的患者可达到完全缓解 [70] .…”