Exo-Linker: Positional Reconfiguration Driving Significant Advances in ADC Stability and Efficacy DOI Open Access

Tomohiro Watanabe,

Tomohiro Fujii,

Yutaka Matsuda

и другие.

ADC Review / Journal of Antibody-drug Conjugates, Год журнала: 2024, Номер unknown

Опубликована: Дек. 30, 2024

Antibody-drug conjugates (ADCs) have transformed targeted cancer therapy by combining the specificity of monoclonal antibodies with cytotoxic potency small-molecule drugs. However, payload instability, hydrophobicity, and premature cleavage limit their efficacy safety. This study presents Exo-Linker technology as a novel solution to these issues. By repositioning cleavable peptide linkers like Glu-Val-Cit Glu-Glu-Val-Cit at exo-position p-aminobenzyl carbamate moiety, Exo-Linkers improve stability, hydrophilicity, resistance enzymatic degradation. Key findings highlight superior pharmacokinetics, tumor-suppressive efficacy, stability ADCs in preclinical models, significantly outperforming traditional Val-Cit-based linkers. Integration second-generation AJICAP platform broadens therapeutic windows, ensures precise drug-to-antibody ratio control, minimizes aggregation. establish new standard for ADC development, overcoming critical limitations while enabling safer more effective treatments. innovative approach redefines landscape, enhances patient outcomes, scope applications.

Язык: Английский

Antibody Modification via Lipoic Acid Ligase A‐Mediated Site‐Specific Labeling DOI
Shunsuke Yamazaki, Yutaka Matsuda

Chemistry & Biodiversity, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Abstract Enzymatic modification, particularly utilizing lipoic acid ligase (LplA), has emerged as a transformative approach in biopharmaceuticals, enabling precise and site‐specific protein modifications. This review delves into the innovative applications of LplA antibody modifications, including creation antibody‐drug conjugates (ADCs) advancement tag‐free conjugation techniques. LplA's ability to facilitate incorporation bioorthogonal groups its adaptability various substrates underscores versatility. Key developments include successful generation dual‐labeled antibodies application modifying fragments. Additionally, explores potential for enhance therapeutic efficacy ADCs through improved drug‐to‐antibody ratios payload attachment. The implications these advancements are significant, suggesting that LplA‐mediated modifications could lead more effective targeted antibody‐based therapies. aims provide comprehensive overview role expanding possibilities enzymatic conjugation, setting stage future research clinical applications.

Язык: Английский

Процитировано

1
Exo-Linker: Positional Reconfiguration Driving Significant Advances in ADC Stability and Efficacy DOI Open Access

Tomohiro Watanabe,

Tomohiro Fujii,

Yutaka Matsuda

и другие.

ADC Review / Journal of Antibody-drug Conjugates, Год журнала: 2024, Номер unknown

Опубликована: Дек. 30, 2024

Antibody-drug conjugates (ADCs) have transformed targeted cancer therapy by combining the specificity of monoclonal antibodies with cytotoxic potency small-molecule drugs. However, payload instability, hydrophobicity, and premature cleavage limit their efficacy safety. This study presents Exo-Linker technology as a novel solution to these issues. By repositioning cleavable peptide linkers like Glu-Val-Cit Glu-Glu-Val-Cit at exo-position p-aminobenzyl carbamate moiety, Exo-Linkers improve stability, hydrophilicity, resistance enzymatic degradation. Key findings highlight superior pharmacokinetics, tumor-suppressive efficacy, stability ADCs in preclinical models, significantly outperforming traditional Val-Cit-based linkers. Integration second-generation AJICAP platform broadens therapeutic windows, ensures precise drug-to-antibody ratio control, minimizes aggregation. establish new standard for ADC development, overcoming critical limitations while enabling safer more effective treatments. innovative approach redefines landscape, enhances patient outcomes, scope applications.

Язык: Английский

Процитировано

0