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HER2-Specific Targeted Toxin DARPin-LoPE: Immunogenicity and Antitumor Effect on Intraperitoneal Ovarian Cancer

Evgeniya A Sokolova1,2, Olga N Shilova3, Daria V Kiseleva4

  • 1Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., Nizhny Novgorod 603950, Russia. malehanova@mail.ru.

International Journal of Molecular Sciences
|May 18, 2019
PubMed

Insights

A novel targeted toxin, DARPin-LoPE, effectively treats HER2-positive ovarian cancer xenografts. This therapeutic agent shows low toxicity and immunogenicity, offering promise for targeted cancer therapy.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • * Pseudomonas aeruginosa exotoxin A-based agents face challenges due to high immunogenicity and systemic toxicity.
  • * Clinical application of these agents is limited by adverse effects and immune responses.

Purpose of the Study:

  • * To evaluate the immunogenicity, general toxicity, and antitumor efficacy of the targeted toxin DARPin-LoPE.
  • * To assess DARPin-LoPE's potential for targeted therapy in HER2-positive tumors.

Main Methods:

  • * Development of DARPin-LoPE, combining a HER2-specific DARPin with a modified, low-immunogenic exotoxin A fragment.
  • * Assessment of antitumor effect on HER2-positive human ovarian carcinoma xenografts.
  • * Evaluation of general toxicity, side effects (vascular leak syndrome, liver degradation), and immunogenicity (specific antibody titer).

Main Results:

  • * DARPin-LoPE demonstrated effective inhibition of HER2-positive ovarian carcinoma xenograft growth.
  • * The targeted toxin exhibited low non-specific toxicity and minimal side effects.
  • * Low immunogenicity was confirmed by specific antibody titer measurements.

Conclusions:

  • * DARPin-LoPE shows significant promise as a targeted therapeutic agent for HER2-positive tumors.
  • * Its favorable safety profile and efficacy suggest potential for clinical application.
  • * This targeted toxin represents a potential advancement in cancer therapy.
Keywords:
DARPinHER2Pseudomonas exotoxin Afar-red fluorescent proteinimmunogenicityovarian carcinomatargeted therapy

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