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Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics DCAF
Published on: September 17, 2019
A humanized chimeric antibody Hai178 targeted to the β subunit of F1F0 ATP synthase
Chen Chen1, Hui Liang2, Xinmei Liao3
1Translational Research Center, Second Hospital, The Second Clinical School, Nanjing Medical University, Nanjing, China.
Abstract:
Inhibition of tumor vasculature is an effective strategy for cancer therapy. Angiostatin could suppress tumor growth and metastasis by binding and inhibiting F1F0 ATP synthase on the endothelial cell surface. We previously screened a monoclonal antibody (McAb, McAb178-5G10), which specifically bound to ATPase on the surface of cells and showed an angiostatin-like activity. Here, we further generated a panel of CHO-mAb subclone stable expressing a humanized chimeric antibody from hybridoma cell McAb178-5G10 by gene engineer. And then, we successfully expressed the humanized antibody Hai178 at high level in a 5-L wave bioreactor. The vitro results showed that Hai178 retained the specific binding and antitumor activity of murine antibody. Furthermore, Hai178 also had a tumor therapeutic effect in tumor xenografts. These results paved the way for Hai178 as a therapeutic antibody in clinic.
Insights
A novel humanized antibody, Hai178, targets tumor vasculature by inhibiting ATP synthase, showing potent anti-tumor effects in preclinical models. This antibody demonstrates promise for future cancer therapies.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Tumor vasculature inhibition is a key cancer therapy strategy.
- Angiostatin inhibits tumor growth by targeting endothelial F1F0 ATP synthase.
- A murine monoclonal antibody (McAb178-5G10) demonstrated angiostatin-like activity by binding cell surface ATPase.
Purpose of the Study:
- To generate and characterize a humanized antibody (Hai178) with angiostatin-like activity.
- To evaluate the therapeutic potential of Hai178 in preclinical cancer models.
Main Methods:
- Gene engineering of hybridoma cells to produce a humanized chimeric antibody (Hai178).
- High-level expression of Hai178 in a 5-L wave bioreactor.
- In vitro assessment of Hai178 binding specificity and anti-tumor activity.
- In vivo evaluation of Hai178 efficacy in tumor xenograft models.
Main Results:
- Hai178 successfully expressed at high levels.
- In vitro studies confirmed Hai178 retains specific binding and anti-tumor activity.
- Hai178 demonstrated significant therapeutic effects in tumor xenografts.
Conclusions:
- The humanized antibody Hai178 retains the therapeutic properties of its murine counterpart.
- Hai178 shows potential as a clinical therapeutic antibody for cancer treatment.
- These findings support the advancement of Hai178 towards clinical trials.

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