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Blinatumomab 治疗 B 细胞前体急性淋巴细胞白血病患者中 T 细胞淋巴细胞动力学监测的潜在临床影响:单中心经验。

Potential clinical impact of T-cell lymphocyte kinetics monitoring in patients with B cell precursors acute lymphoblastic leukemia treated with blinatumomab: a single-center experience.

机构信息

Division of Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Postgraduate School of Hematology, University of Catania, Catania, Italy.

出版信息

Front Immunol. 2023 Sep 22;14:1195734. doi: 10.3389/fimmu.2023.1195734. eCollection 2023.

Abstract

Blinatumomab is a bispecific anti-CD3 and anti-CD19 antibody that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target the cancer cells. Here we describe seven different patients affected by B-cell precursor acute lymphoblastic leukemia (Bcp-ALL) and treated with blinatumomab, on which we evaluated the potential association between the amount of different T-cells subsets and deep molecular response after the first cycle, identified as a complete remission in the absence of minimal residual disease (CR/MRD). The immune-system effector cells studied were CD3+, CD4+ effector memory (T4-EM), CD8+ effector memory (T8-EM), and T-regulatory (T-reg) lymphocytes, and myeloid-derived suppressor cells (MDSC). Measurements were performed in the peripheral blood using flow cytometry of the peripheral blood at baseline and after the first cycle of blinatumomab. The first results show that patients with a higher proportion of baseline T-lymphocytes achieved MRD negativity more frequently with no statistically significant difference (p=0.06) and without differences in the subpopulation count following the first treatment. These extremely preliminary data could potentially pave the way for future studies, including larger and less heterogeneous cohorts, in order to assess the T-cell kinetics in a specific set of patients with potential synergy effects in targeting myeloid-derived suppressor cells (MDSC), commonly known to have an immune evasion mechanism in Bcp-ALL.

摘要

Blinatumomab 是一种双特异性抗 CD3 和抗 CD19 的抗体,作为一种 T 细胞衔接器:通过结合 CD19+淋巴母细胞,blinatumomab 招募细胞毒性 CD3+T 淋巴细胞来靶向癌细胞。在这里,我们描述了 7 名不同的 B 细胞前体急性淋巴细胞白血病(Bcp-ALL)患者接受了 blinatumomab 治疗,并评估了在第一个周期后,不同 T 细胞亚群数量与深度分子反应之间的潜在关联,该反应被定义为无微小残留病(MRD)的完全缓解(CR/MRD)。研究的免疫系统效应细胞包括 CD3+、CD4+效应记忆(T4-EM)、CD8+效应记忆(T8-EM)和 T 调节(T-reg)淋巴细胞以及髓源性抑制细胞(MDSC)。使用外周血中的流式细胞术在基线和 blinatumomab 第一个周期后测量外周血中的这些免疫细胞。初步结果表明,基线时 T 淋巴细胞比例较高的患者更容易实现 MRD 阴性,差异无统计学意义(p=0.06),并且在第一次治疗后,亚群计数没有差异。这些极其初步的数据可能为未来的研究铺平道路,包括更大和更少异质性的队列,以评估特定患者群体中的 T 细胞动力学,并有可能在靶向髓源性抑制细胞(MDSC)方面产生协同效应,这些细胞通常在 Bcp-ALL 中具有免疫逃避机制。

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