Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4.
Oncogene
; 43(29): 2244-2252, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38806619
ABSTRACT
The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Bispecific
/
CTLA-4 Antigen
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Programmed Cell Death 1 Receptor
/
Single-Domain Antibodies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: