Humanization and characterization of an anti-ciguatoxin CTX3C monoclonal antibody.
Toxicon
; 247: 107848, 2024 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-38964619
ABSTRACT
Ciguatera poisoning (CP), caused by ciguatoxins (CTXs), is one of the most common food-borne diseases, affecting more than 50,000 people each year. In most cases, CP are managed with symptomatic and supportive remedies, and no specific treatment has been devised. In this study, toward the development of therapeutic antibodies for CP, we examined to humanize mouse anti-CTX3C antibody 10C9 (m10C9), which exhibited neutralizing activity against ciguatoxin in vitro and in vivo. The complementarity determining regions were grafted onto a human germline sequence with high sequence identity to m10C9, and the backmutations were examined to maintain the binding affinity. The optimized humanized antibody, Opt.h10C9Fab, showed a strong binding affinity to CTX3C with a high affinity (KD = 19.0 nM), and only two backmutations of ArgL46 and CysH94 in the framework regions were involved in determining the antigen binding affinity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ciguatoxins
Limits:
Animals
/
Humans
Language:
En
Journal:
Toxicon
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: