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This study mainly explored the anti-tumor effects of programmed death ligand 1/ transforming growth factor-β (PD-L1/TGF-β) bispecific antibody drugs in the huHSC-NCG mouse brain orthotopic transplantation model of human glioma cell U251-luciferase (all animal experiments in this study were approved by the Experimental Animal Ethics Committee of GemPharmatech, and the ethics review number is GPTAP20230706-3). The antibody-antigen binding activity of the PD-L1/TGF-β bispecific antibody drugs to PD-L1 target on U251 cells was detected by flow cytometry in vitro. The antitumor activity of PD-L1/TGF-β bispecific antibody drugs was evaluated using a brain glioma in orthotopic implantation model with humanized immune system. Live animal imaging and brain tissue (including tumor tissue) weight results showed that the PD-L1/TGF-β dual antibody drug had an inhibitory effect on the growth of glioma in situ. The results of drug content (ELISA assay) and drug distribution (immunohistochemistry assay) in brain tissue showed that PD-L1/TGF-β dual antibody could enter the brain glioma and play the function of immune checkpoint, thus playing an inhibitory role in brain glioma. Immunofluorescence staining of mouse brain tissue showed that the drug activated the immune system and had synergistic anti-tumor effect with the immune system. These results showed that the PD-L1/TGF-β bispecific antibody drugs have broken through the blood-tumor barrier in orthotopic implantation model of mouse brain glioma and demonstrated a strong anti-tumor effect. In conclusion, the inhibitory effects of PD-L1/TGF-β bispecific antibody drugs on human brain glioma provides a new strategy for the treatment of human brain glioma.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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