放射性核素药物结合物（RDCs）与抗体构成了治疗包括胶质母细胞瘤在内的恶性肿瘤的新方法。然而，RDCs需要适宜的抗体才能发挥高效作用。Hu4G4是一种新型的靶向B7-H3的人源化单克隆IgG1抗体，具有高度特异性对人B7-H3蛋白（包括胶质母细胞瘤细胞）的识别能力。在本研究中，我们建立了131I标记的hu4G4（131I-hu4G4），并显示它与B7-H3具有高亲和力结合（Kd = 0.99 ± 0.07 nM），并且能够在体外抑制U87细胞的生长。根据GL261 Red-Fluc-B7-H3细胞的小鼠胶质瘤模型，131I-hu4G4展示了强效的原位抗肿瘤活性。更重要的是，131I-hu4G4重塑了肿瘤微环境，促进了胶质瘤由“冷”型向“热”型转化，通过促进CD4+和CD8+T细胞浸润以及M2向M1的极化。因此，使用131I-hu4G4观察到的抗肿瘤活性以及其增强抗肿瘤免疫应答的能力，使得它成为胶质母细胞瘤放射免疫治疗的新候选物。© 作者中（们）

Radionuclide drug conjugates (RDCs) with antibodies serve as a novel approach for the treatment of malignant tumors including glioblastoma. However, RDCs require optimal antibodies to work efficiently. Hu4G4, a novel B7-H3-targeting humanized monoclonal IgG1 antibody, is highly specific for the human B7-H3 protein (a marker of tumor cells, including glioblastoma cells). Herein, we established 131I-labeled hu4G4 (131I-hu4G4) and showed that it specifically bound to B7-H3 with high affinity (Kd = 0.99 ± 0.07 nM) and inhibited the growth of U87 cells in vitro. 131I-hu4G4 displayed potent in situ antitumor activity in a mouse model of glioma based on GL261 Red-Fluc-B7-H3 cells. More importantly, 131I-hu4G4 remodeled the tumor microenvironment and promoted the transformation of glioma from "cold" to "hot" tumors by promoting CD4+ and CD8+ T cell infiltration and the polarization of M2 to M1. Therefore, the antitumor activity observed with 131I-hu4G4, together with its ability to enhance antitumor immune responses, makes it a novel candidate for radioimmunotherapy of glioblastoma.© The author(s).