Zou Haoyong, Yin Wenqu, Geng Peng, Lin Li, Nie Xilin, Tao Zui, Chen Gang, Chen Bin, Feng Hao, Xu Kuanhong, Zhang Zhi
YuJin Biological Basic research laboratory, Wuhan Institute of Biological Products, Wuhan, 430207, Hubei, China.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Ann Hematol. 2025 Jan;104(1):761-771. doi: 10.1007/s00277-024-06028-9. Epub 2024 Oct 15.
Anti-human T lymphocyte porcine immunoglobulin (p-ATG) is a potent immunosuppressive agent derived from porcine sources used in various immunotherapy applications. It is compared with similar products derived from other species, such as rabbit anti-thymocyte globulin (r-ATG) and ATG-Fresenius (ATG-F), which have distinct biological and therapeutic properties. This study aims to elucidate the mechanisms of action and comparative efficacy of p-ATG in relation to r-ATG and ATG-F through a comprehensive in vitro analysis.
A comparative analysis of p-ATG, r-ATG and ATG-F was performed, focusing on E rosette inhibitory potency, lymphocyte toxic potency, blocking activities of 24 CD molecules, and flow quantitative potency. Flow cytometric analysis was used to quantify these characteristics and assess the potency of the immunoglobulins.
p-ATG exhibited lower E rosette inhibitory and lymphocyte toxic potencies compared to r-ATG but was significantly more potent than ATG-F at equivalent concentrations. At protein concentrations above 12.5 µg/mL, p-ATG showed slightly lower potency than r-ATG and much higher potency than ATG-F in flow cytometry assays. Both p-ATG and r-ATG exhibited similar killing effects on lymphocytes within the peripheral blood mononuclear cells (PBMCs), including CD3 + T cells, with a dose-dependent response. Notably, p-ATG displayed more pronounced blocking activities against CD8, CD99, and TCR α/β compared to r-ATG.
p-ATG offers certain advantages over r-ATG and ATG-F, particularly in its ability to inhibit specific CD molecules and its overall potency in immunosuppressive assays, providing valuable insights for assisting clinical decision-making regarding the selection of ATG types based on patient-specific needs and treatment objectives.
抗人T淋巴细胞猪免疫球蛋白(p - ATG)是一种强效免疫抑制剂,来源于猪,用于各种免疫治疗应用。它与其他物种来源的类似产品进行了比较,如兔抗胸腺细胞球蛋白(r - ATG)和费森尤斯抗胸腺细胞球蛋白(ATG - F),这些产品具有不同的生物学和治疗特性。本研究旨在通过全面的体外分析阐明p - ATG相对于r - ATG和ATG - F的作用机制和比较疗效。
对p - ATG、r - ATG和ATG - F进行了比较分析,重点关注E花环抑制效力、淋巴细胞毒性效力、24种CD分子的阻断活性和流式定量效力。采用流式细胞术分析来量化这些特征并评估免疫球蛋白的效力。
与r - ATG相比,p - ATG表现出较低的E花环抑制和淋巴细胞毒性效力,但在等效浓度下明显比ATG - F更有效。在蛋白质浓度高于12.5μg/mL时,在流式细胞术检测中,p - ATG的效力略低于r - ATG,但远高于ATG - F。p - ATG和r - ATG对外周血单个核细胞(PBMC)中的淋巴细胞,包括CD3 + T细胞,均表现出相似的杀伤作用,呈剂量依赖性反应。值得注意的是,与r - ATG相比,p - ATG对CD8、CD99和TCRα/β表现出更明显的阻断活性。
与r - ATG和ATG - F相比,p - ATG具有一定优势,特别是在抑制特定CD分子的能力及其在免疫抑制检测中的总体效力方面,为根据患者特定需求和治疗目标选择ATG类型的临床决策提供了有价值的见解。