Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms20102399
Keywords
targeted therapy; DARPin; Pseudomonas exotoxin A; immunogenicity; ovarian carcinoma; HER2; far-red fluorescent protein
Funding
- Russian Foundation for Basic Research [17-00-00122, 17-00-00119, 17-00-00121]
- Russian Science Foundation [19-74-20168]
- Ministry of Science and Higher Education [6.7109.2017/9.10]
- Russian Science Foundation [19-74-20168] Funding Source: Russian Science Foundation
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High immunogenicity and systemic toxicity are the main obstacles limiting the clinical use of the therapeutic agents based on Pseudomonas aeruginosa exotoxin A. In this work, we studied the immunogenicity, general toxicity and antitumor effect of the targeted toxin DARPin-LoPE composed of HER2-specific DARPin and a low immunogenic exotoxin A fragment lacking immunodominant human B lymphocyte epitopes. The targeted toxin has been shown to effectively inhibit the growth of HER2-positive human ovarian carcinoma xenografts, while exhibiting low non-specific toxicity and side effects, such as vascular leak syndrome and liver tissue degradation, as well as low immunogenicity, as was shown by specific antibody titer. This represents prospects for its use as an agent for targeted therapy of HER2-positive tumors.
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