Abstract
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.
Highlights
Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China; Jecho Biopharmaceuticals Co., Ltd
Reaction may interfere with correct folding and antibody structure, the proper reducing condition was screened for generating EGFRvIII-BsAb (Figure 2c)
The final product of EGFRvIII-BsAb was polished with an MMC ImpRes Multimodal Chromatography Column (Figure 2e), and was characterized with LC/MS and Surface Plasmon Resonance (SPR)
Summary
Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China; Jecho Biopharmaceuticals Co., Ltd. The results demonstrated the antitumor potential and long circulation time of EGFRvIII-BsAb in NOD/SCID mice bearing de subcutaneously heterotopic transplantation tumors and BALB/c mice. 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. 1. Introduction with regard to jurisdictional claims in GBM is a highly malignant tumor that originates in the central nervous system (CNS). Introduction with regard to jurisdictional claims in GBM is a highly malignant tumor that originates in the central nervous system (CNS) It accounts for 54% of all gliomas and 16% of all primary brain tumors [1]. The current standard of care is still external irradiation after maximum safe resection, treatment with temozolomide (TMZ), and maintenance chemotherapy [4,5]
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