276治疗性抗体对脑胶质瘤的研究

o develop a humanized Fc segment mutant recombinant antibody targeting CD276 positive gliomas and further evaluate its efficacy in vitro; Evaluate the inhibitory effect of this antibody on glioma in vivo. Method: The Fc glycosylation site F243L/R292P/Y300L/V305I/P396L of humanized CD276 antibody was mutated, and the obtained sequence was introduced into CHO cells through gene synthesis. The cell supernatant was collected and purified; Validate its effectiveness through luciferase expression levels in the Jurkat-NFAT-Luciferase-CD16 platform; Reconstruct NK cells through peripheral blood mononuclear cells (PBMCs) in humanized mice and validate their inhibitory effect on U-87 MG glioma in vivo. 3. Result: Two humanized antibodies were obtained after successfully mutating the Fc glycosylation site: CD276T1H1L1 Fc mut and CD276T2H1L1 Fc mut antibodies; In the Jurkat-NFAT Luciferase CD16Fc platform, the ADCC effect of Fc mutated antibodies was significantly increased compared to unmodified antibodies; In PBMC humanized mice, the CD276T1H1L1 Fc mut group exhibited good anti-tumor effects in a dose-dependent manner. Conclusion: The CD276 recombinant antibody with Fc mutation has good efficacy in vitro; In humanized mouse models, the CD276 recombinant antibody with Fc mutation showed good anti-tumor effects.