A Rational Designed Novel Bispecific Antibody for the Treatment of GBM

• Published in: Biomedicines Vol. 9; no. 6; p. 640
• Main Authors: Sun, Rui, Zhou, Yuexian, Han, Lei, Pan, Zhidi, Chen, Jie, Zong, Huifang, Bian, Yanlin, Jiang, Hua, Zhang, Baohong, Zhu, Jianwei
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 03.06.2021; MDPI
• Subjects: Animal models; Antibodies; Antigens; Antitumor activity; Binding sites; Bispecific antibodies; bispecific antibody; Brain cancer; Cancer immunotherapy; Chemotherapy; Chromatography; Cytokines; Cytotoxicity; Effector cells; EGFRvIII; Epidermal growth factor; Flow cytometry; GBM; Glioblastoma; High-performance liquid chromatography; Immunodeficiency; Immunogenicity; Immunotherapy; Laboratories; Lymphocytes; Lymphocytes T; Medical prognosis; Pharmacokinetics; Proteins; split intein; Therapeutic targets; Transplantation; Tumors; Chicago Illinois; St Louis Missouri; United States > US; China
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9060640

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.