Your browser doesn't support javascript.
loading
Rational Identification of Novel Antibody-Drug Conjugate with High Bystander Killing Effect against Heterogeneous Tumors.
Guo, Yu; Shen, Zheyuan; Zhao, Wenbin; Lu, Jialiang; Song, Yi; Shen, Liteng; Lu, Yang; Wu, Mingfei; Shi, Qiuqiu; Zhuang, Weihao; Qiu, Yueping; Sheng, Jianpeng; Zhou, Zhan; Fang, Luo; Che, Jinxin; Dong, Xiaowu.
Afiliación
  • Guo Y; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Shen Z; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Zhao W; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, P. R. China.
  • Lu J; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Song Y; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Shen L; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Lu Y; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Wu M; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Shi Q; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Zhuang W; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Qiu Y; The Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
  • Sheng J; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, P. R. China.
  • Zhou Z; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, P. R. China.
  • Fang L; The Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
  • Che J; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
  • Dong X; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Adv Sci (Weinh) ; 11(13): e2306309, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38269648
ABSTRACT
Bystander-killing payloads can significantly overcome the tumor heterogeneity issue and enhance the clinical potential of antibody-drug conjugates (ADC), but the rational design and identification of effective bystander warheads constrain the broader implementation of this strategy. Here, graph attention networks (GAT) are constructed for a rational bystander killing scoring model and ADC construction workflow for the first time. To generate efficient bystander-killing payloads, this model is utilized for score-directed exatecan derivatives design. Among them, Ed9, the most potent payload with satisfactory permeability and bioactivity, is further used to construct ADC. Through linker optimization and conjugation, novel ADCs are constructed that perform excellent anti-tumor efficacy and bystander-killing effect in vivo and in vitro. The optimal conjugate T-VEd9 exhibited therapeutic efficacy superior to DS-8201 against heterogeneous tumors. These results demonstrate that the effective scoring approach can pave the way for the discovery of novel ADC with promising bystander payloads to combat tumor heterogeneity.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoconjugados Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoconjugados Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article Pais de publicación: Alemania