title: A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas.
abstract: Antibody-based targeted therapy of cancers requires the antibody targeting of specific molecules inducing tumor cells apoptosis or death. Angiopoietin-2 (Agn-2) and translocator protein (TSPO) are identified as potential target molecules for glioblastoma therapy. The single chain anti-Agn-2 antibody (Anag-2) and anti-TSPO antibody (ATSPO) were obtained by monoclonal antibody screening. In the present study, for specific targeting and killing, we generated a recombinant bispecific antibody comprising a single-chain Fragment variable (ScFv) of anti-human Agn-2 and anti-human TSPO (ScBsAbAgn-2/TSPO), which is the mediator for mitochondrial apoptosis and tumor angiogenesis. In vitro, ScBsAbAgn-2/TSPO simultaneously bounded to both targets with a high antigen-binding affinity to Anag-2 and TSPO compared to the individual antibody. The higher expression of Ang-2 and TSPO was observed in bevacizumab-treated glioblastoma compared to normal rat brain endothelium. We also observed apoptosis-mediated cytotoxicity was improved, which resulted in the elimination of up to 90% of the target cells within 72 h. ScBsAbAgn-2/TSPO inhibited tumor growth, decreased vascular permeability, led to extended survival, improved pericyte coverage, depletion of tumor-associated macrophages, and increased numbers of intratumoral T lymphocytes infiltration in a murine bevacizumab-treated glioblastoma model. These findings were also confirmed ex vivo using glioblastoma cells from bevacizumab-treated rats with glioblastoma. We conclude that ScBsAbAgn-2/TSPO targeting of glioblastoma cell lines can be achieved in vitro and in vivo that the efficient elimination of glioblastoma cells supports the potential of ScBsAbAgn-2/TSPO as a potent, novel immunotherapeutic agent.
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Lianjie
authors.initials: L
authors.lastname: Lv
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Xiuju
authors.initials: X
authors.lastname: Chen
authors.affiliation: Surgical Department, Tianjin Nankai Hospital, Tianjin, 300100, China. Electronic address: zhoushengnian1967@126.com.
authors.forename: Changlin
authors.initials: C
authors.lastname: Zou
mesh_terms: D042702:Angiopoietin-2 / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D018079:Receptors, GABA / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D000911:Antibodies, Monoclonal; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: Agn-2; Glioblastoma; ScBsAbAgn-2/TSPO; TSPO; Targeted therapy