A Rational Designed Novel Bispecific Antibody for the Treatment of GBM.
A Rational Designed Novel Bispecific Antibody for the Treatment of GBM.
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合理设计的新型双特异性抗体用于治疗 GBM
DOI：
10.3390/biomedicines9060640
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发表时间：
2021-06-03
期刊：
影响因子：
4.7
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Sun R;Zhou Y;Han L;Pan Z;Chen J;Zong H;Bian Y;Jiang H;Zhang B;Zhu J
Epidermal growth factor receptor variant III (EGFRvIII) is highly and specifically expressed in a subset of lethal glioblastoma (GBM), making the receptor a unique therapeutic target for GBM. Recently, bispecific antibodies (BsAbs) have shown exciting clinical benefits in cancer immunotherapy. Here, we report remarkable results for GBM treatment with a BsAb constructed by the “BAPTS” method. The BsAb was characterized through LC/MS, SEC-HPLC, and SPR. Furthermore, the BsAb was evaluated in vitro for bioactivities through FACS, antigen-dependent T-cell-mediated cytotoxicity, and a cytokine secretion assay, as well as in vivo for antitumor activity and pharmacokinetic (PK) parameters through immunodeficient NOD/SCID and BALB/c mouse models. The results indicated that the EGFRvIII-BsAb eliminated EGFRvIII-positive GBM cells by recruiting and stimulating effector T cells secreting cytotoxic cytokines that killed GBM cells in vitro. The results demonstrated the antitumor potential and long circulation time of EGFRvIII-BsAb in NOD/SCID mice bearing de2–7 subcutaneously heterotopic transplantation tumors and BALB/c mice. In conclusion, our experiments in both in vitro and in vivo have shown the remarkable antitumor activities of EGFRvIII-BsAb, highlighting its potential in clinical applications for the treatment of GBM. Additional merits, including a long circulation time and low immunogenicity, have also made the novel BsAb a promising therapeutic candidate.
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影响因子：
10.9
作者：
Groeneveldt C;Kinderman P;van den Wollenberg DJM;van den Oever RL;Middelburg J;Mustafa DAM;Hoeben RC;van der Burg SH;van Hall T;van Montfoort N
通讯作者：
van Montfoort N
影响因子：
5.7
作者：
Mandikian, Danielle;Takahashi, Nene;Boswell, C. Andrew
通讯作者：
Boswell, C. Andrew
影响因子：
20.3
作者：
Klinger, Matthias;Brandl, Christian;Kufer, Peter
通讯作者：
Kufer, Peter
影响因子：
50.5
作者：
Neyns, B.;Sadones, J.;De Greve, J.
通讯作者：
De Greve, J.
DOI：
10.1158/1078-0432.ccr-17-0126
发表时间：
2018-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gedeon PC;Schaller TH;Chitneni SK;Choi BD;Kuan CT;Suryadevara CM;Snyder DJ;Schmittling RJ;Szafranski SE;Cui X;Healy PN;Herndon JE 2nd;McLendon RE;Keir ST;Archer GE;Reap EA;Sanchez-Perez L;Bigner DD;Sampson JH
通讯作者：
Sampson JH