RESUMO
@# CD47是细胞表面高度糖化的穿膜蛋白，是一种“别吃我”信号，可与信号调节蛋白α（SIRPα）等形成CD47-SIRPα抑制 信号复合体，从固有免疫和适应性免疫两方面同时逃避机体的免疫监视。研究发现，CD47在血液肿瘤和多种实体瘤中高表达， 通过与巨噬细胞上的SIRPα配体结合，启动一系列抑制性的信号转导而躲避吞噬，其高水平表达既能促进肿瘤细胞的生长又能 促进肿瘤细胞的转移。通过抗CD47抗体阻断CD47-SIRPα信号通路，达到抑制肿瘤细胞的免疫逃逸，增强巨噬细胞的吞噬作用 和适应性免疫应答，是免疫治疗肿瘤的新途径。目前，国内外开展了越来越多靶向CD47-SIRPα的药物或抗体的基础研究和临床 试验，有望从抗体分子设计和重组蛋白等方面解决靶向CD47抗肿瘤治疗时发生的贫血和输液相关不良反应等问题。本文就 CD47的分子结构与生理功能、CD47-SIRPα表达调控机制、CD47抗肿瘤治疗研究现状以及靶向CD47导致的相关生物安全性问 题和解决方案等方面进行综述， 为CD47新靶点的基础研究和临床应用提供参考。
RESUMO
ABSTRACT To establish a transfusion-associated graft-versus-host disease (TA-GVHD) mouse model with busulfan and fludarabine for effective treatment evaluation. BALB/c (H-2d) mice were injected with busulfan (15 mg/kg) and fludarabine (30 mg/kg) twice a day for 4 days. The mice were transfused with 106 T cell-depleted bone marrow (TCD-BM )and cells in different groups 3 days after chemotherapy: syngeneic BALB/c, MHC minor mismatch DBA/2 (H-2d), or MHC major mismatch C57BL/6(H2-b). Recipient BALB/c mice were injected with either blood only or blood+splenocyte. TA-GVHD was monitored in terms of body weight loss, clinical scores, and survival. Dexamethasone (50 mg/kg), cyclophosphamide (50 mg/kg), cyclosporine A (30 mg/kg), and anti-CD3 (1 mg/kg) were injected to each group to examine the treatments. Blood transfusion alone is insufficient to induce TA-GVHD in a chemotherapy-based mouse model. A MHC-mismatched TA-GVHD model can be induced by splenocyte and blood transfusion. This MHC-mismatched TA-GVHD model was resistant to dexamethasone treatment. Treatment based on anti-CD3 monoclonal antibody slightly ameliorated TA-GVHD. Treatment effectiveness was associated with T-cell depletion following activation by anti-CD3. Busulfan and fludarabine chemotherapy regimen can be used to establish a TA-GVHD mouse model. Anti-CD3 monoclonal antibody is a potential alternative to treat TA-GVHD.