Centro de Investigaciones Biologicas Margarita Salas (CIB-CSIC), Department of Molecular Medicine, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Centro Nacional de Biotecnología (CNB-CSIC), Department of Immunology and Oncology, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Front Immunol. 2022 Jul 27;13:825635. doi: 10.3389/fimmu.2022.825635. eCollection 2022.
Relapsed or refractory T acute lymphoblastic leukemia (T-ALL) still carries poor prognosis. Aiming to improve outcomes, the therapeutic potential of an anti-CCR9 monoclonal antibody (mAb 92R), targeting the human chemokine-receptor CCR9 is analyzed on orthotopic xenotransplants. 92R mAb treatment of mice carrying human CCR9 T-ALL cell lines or primary T cell leukemias inhibits tumor growth and increases survival. The therapeutic effects of 92R are specific and synergize with chemotherapeutic agents increasing survival. Furthermore, 92R decreases size of non-hematopoietic tumors with a forced CCR9 expression and of solid tumors generated by the pancreatic adenocarcinoma cell line AsPC-1. In addition, a humanized version of 92R mAb (Srb1) is also able to inhibit growth of CCR9 T-ALL tumor cells , increasing survival 2.66-fold. Finally, 92R mAb prevents liver accumulation of infiltrates and reduces tumor cell numbers in already formed infiltrates. Thus, the humanized version of 92R mAb (Srb1), displays therapeutic potential for CCR9 tumor treatment and might represent one of the first therapeutic antibodies for precision medicine on T-ALL patients.
复发或难治性 T 急性淋巴细胞白血病 (T-ALL) 预后仍然较差。为了改善预后，针对人类趋化因子受体 CCR9 的抗 CCR9 单克隆抗体 (mAb 92R) 的治疗潜力在原位异种移植中进行了分析。92R mAb 治疗携带人 CCR9 T-ALL 细胞系或原发性 T 细胞白血病的小鼠可抑制肿瘤生长并提高存活率。92R 的治疗效果是特异性的，并与化疗药物协同作用，提高存活率。此外，92R 可减小具有强制 CCR9 表达的非造血肿瘤和由胰腺腺癌细胞系 AsPC-1 产生的实体瘤的大小。此外，人源化的 92R mAb (Srb1) 也能够抑制 CCR9 T-ALL 肿瘤细胞的生长，使存活率提高 2.66 倍。最后，92R mAb 可防止浸润物在肝脏中的积累，并减少已形成的浸润物中的肿瘤细胞数量。因此，人源化的 92R mAb (Srb1) 显示出用于 CCR9 肿瘤治疗的治疗潜力，并且可能成为 T-ALL 患者精准医学的首批治疗性抗体之一。
