ArticleAntibody therapeutics2025
Overcoming antigen tolerance to develop GB22-45-2, an anti-DKK1 antibody for gastric cancer.
Article in Antibody therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- LncRNA DNAJC3-AS1 promotes gastric cancer malignancy through miR-576-5p-mediated upregulation of LYPLA1.American journal of cancer research · 2026Article
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11 authors.
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Abstract
Background: Gastric cancer (GC) represents one of the most prevalent and lethal malignancies, however, current treatments have shown limited efficacy. Clinical investigations have revealed that Dickkopf-1 (DKK1)-high GC patients are associated with poor prognosis, and DKK1 expression is negatively correlated with overall survival, suggesting a means of pharmaceutical intervention by neutralizing DKK1 for GC patients. Methods: To overcome antigen tolerance and stimulate antibody production, strategies were employed, including different adjuvants, antigen design, and various mouse strains. Finally, a novel antibody targeting DKK1 was screened out from ~100 000 candidates. GB22-45-2 underwent Results: GB22-45 screened out from Murphy Roths Large (MRL/MpJ) mice immunized with Freund's adjuvant and full-length DKK1 conjugated with Keyhole Limpet Hemocyanin achieved the best affinity. C34V and M99V mutations were introduced to the final optimized humanized antibody, GB22-45-2, to prevent dimer formation and mitigate risks of methionine oxidation. Conclusions: In summary, these preclinical results suggest that GB22-45-2 is a potential therapeutic candidate for GC, laying the foundation for its future drug development.
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