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.

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.