1 Center for Molecular Medicine Cologne (CMMC), University of Cologne, and Deparment I for Internal Medicine, University Hospital Cologne , Cologne, Germany.
2 Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karls University , Tübingen, Germany.
Hum Gene Ther. 2017 Dec;28(12):1147-1157. doi: 10.1089/hum.2017.126.
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells that lack the CAR targeted antigen. In this situation, a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T-cell activation. T cells with the anti-CD20-CD19 CAR efficiently killed patients' chronic lymphocytic leukemia cells in vitro. The bispecific CAR T cells cleared pediatric acute lymphocytic leukemia with a mixed CD19CD20/CD20 phenotype from the blood and bone marrow of transplanted mice, while anti-CD20 CAR T cells left CD20 leukemic cells behind without curing the disease. Data indicate the superior anti-leukemic activity in the control of leukemia, implying that the anti-CD20-CD19 bispecific CAR T cells may reduce the risk of relapse through antigen-loss leukemic cells in the long term.
嵌合抗原受体 (CAR) 修饰的 T 细胞对 CD19 的特异性治疗白血病/淋巴瘤,使大多数患者获得完全缓解,有治愈的现实希望。然而,最近的随访数据显示,通过缺乏 CAR 靶向抗原的白血病细胞存在实质性的复发风险。在这种情况下,一种具有结合 CD19 和 CD20 结合域的双特异性 CAR 旨在识别仅具有一个同源抗原的白血病细胞。抗 CD20-CD19 双特异性 CAR 在与靶细胞上的 CD19 或 CD20 结合时诱导完全 T 细胞反应,在重新定向 T 细胞激活方面表现出真正的“或”门识别。具有抗 CD20-CD19 CAR 的 T 细胞在体外有效杀伤患者慢性淋巴细胞白血病细胞。双特异性 CAR T 细胞清除了移植小鼠血液和骨髓中具有混合 CD19CD20/CD20 表型的小儿急性淋巴细胞白血病,而抗 CD20 CAR T 细胞在不治愈疾病的情况下留下了 CD20 白血病细胞。数据表明在控制白血病方面具有更好的抗白血病活性,这意味着抗 CD20-CD19 双特异性 CAR T 细胞可能会降低长期内通过抗原丢失白血病细胞复发的风险。
Hum Gene Ther. 2017-12
Cancer Immunol Res. 2016-4-8
J Immunother Cancer. 2017-5-16
Sci China Life Sci. 2023-4
Front Immunol. 2025-2-28
Biomedicines. 2024-5-28
Clin Transl Oncol. 2024-6