肿瘤细胞治疗研究
英文原题：Current status of BAFF targeting immunotherapy in B-cell neoplasm.
属于 TNF 家族的 B 细胞激活因子（BAFF），也称为 B 淋巴细胞刺激因子（BLyS），在 B 细胞发育中起着至关重要的作用。
属于 TNF 家族的 B 细胞激活因子（BAFF），也称为 B 淋巴细胞刺激因子（BLyS），在 B 细胞发育中发挥关键作用。它具有多个受体，包括 BCMA、TACI 和 BAFF-R，在不同细胞类型中具有多种作用。BAFF 诱导 B 细胞增殖和免疫球蛋白分泌，并作为未成熟、初始和活化 B 细胞的存活因子。因此，BAFF 缺陷小鼠常表现出体液免疫应答受抑，而 BAFF 过表达小鼠则表现出成熟 B 细胞数量增多，并可能发生自身免疫样表现和 B 细胞淋巴增殖性疾病。BAFF 水平升高也与多种血液系统恶性肿瘤相关，其表达在某些情况下与疾病进展相关。因此，针对 BAFF 的疗法，如 belimumab、atacicept 和 tabalumab，正在慢性淋巴细胞白血病（CLL）和多发性骨髓瘤等疾病的临床试验中进行探索。Belimumab 是一种抗 BAFF 单克隆抗体，正在研究其与 rituximab/venetoclax 联合用于 CLL。Atacicept 是 BAFF 和 APRIL 的诱饵受体，在 CLL 的 1b 期试验中显示出耐受性。Tabalumab 是另一种靶向 BAFF 的单克隆抗体，在复发/难治性多发性骨髓瘤的 2 期研究中未显示出显著疗效。基于 BAFF 配体的 CAR-T 细胞被设计用于靶向 BAFF 受体，并在临床前研究中显示出前景，尤其是针对 B 细胞恶性肿瘤。该综述强调了理解 BAFF 及其受体在血液系统恶性肿瘤微环境中作用的重要性。靶向 BAFF 及其受体提供了潜在的治疗途径，正在进行的临床试验提供了有价值的见解。
B-cell activating factor belonging to the TNF family (BAFF), also known as B-lymphocyte stimulator (BLyS), plays a crucial role in B-cell development. It has multiple receptors, including BCMA, TACI, and BAFF-R, with diverse roles in different cell types. BAFF induces B-cell proliferation and immunoglobulin secretion, and acts as a survival factor for immature, naive, and activated B cells. Consequently, BAFF-deficient mice often show suppressed humoral responses, while BAFF-overexpressing mice show the higher number of mature B cells and may develop autoimmune-like manifestations and B-cell lymphoproliferative diseases. Elevated BAFF levels are also associated with various hematological malignancies, and its expression correlates with disease progression in some cases. Therefore, BAFF-targeted therapies, such as belimumab, atacicept, and tabalumab, are being explored in clinical trials for conditions like chronic lymphocytic leukemia (CLL) and multiple myeloma. Belimumab, an anti-BAFF monoclonal antibody, is being investigated in combination with rituximab/venetoclax for CLL. Atacicept, a decoy receptor for BAFF and APRIL, showed tolerability in a phase 1b trial for CLL. Tabalumab, another monoclonal antibody targeting BAFF, did not demonstrate significant efficacy in a phase 2 study for relapsed/refractory multiple myeloma. BAFF ligand-based CAR-T cells are designed to target BAFF receptors and show promise in preclinical studies, particularly for B-cell malignancies. The review emphasizes the importance of understanding the roles of BAFF and its receptors in the microenvironment of hematologic malignancies. Targeting BAFF and its receptors presents potential therapeutic avenues, and ongoing clinical trials provide valuable insights.
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