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Oncolytic herpes simplex virus armed with a bacterial GBP1 degrader improves antitumor activity.
Xie, Jun; Wang, Shaowei; Zhong, Yunhong; Gao, Ming; Tian, Xuezhang; Zhang, Liting; Pan, Dongli; Qin, Qingsong; Wu, Bing; Lan, Ke; Sun, Zhi-Jun; Zhang, Junjie.
Afiliación
  • Xie J; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Wang S; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
  • Zhong Y; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Gao M; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
  • Tian X; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Zhang L; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
  • Pan D; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Qin Q; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
  • Wu B; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Lan K; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
  • Sun ZJ; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan 430071, China.
  • Zhang J; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
Mol Ther Oncolytics ; 29: 61-76, 2023 Jun 15.
Article en En | MEDLINE | ID: mdl-37223114
Oncolytic viruses (OVs) encoding various transgenes are being evaluated for cancer immunotherapy. Diverse factors such as cytokines, immune checkpoint inhibitors, tumor-associated antigens, and T cell engagers have been exploited as transgenes. These modifications are primarily aimed to reverse the immunosuppressive tumor microenvironment. By contrast, antiviral restriction factors that inhibit the replication of OVs and result in suboptimal oncolytic activity have received far less attention. Here, we report that guanylate-binding protein 1 (GBP1) is potently induced during HSV-1 infection and restricts HSV-1 replication. Mechanistically, GBP1 remodels cytoskeletal organization to impede nuclear entry of HSV-1 genome. Previous studies have established that IpaH9.8, a bacterial E3 ubiquitin ligase, targets GBPs for proteasomal degradation. We therefore engineered an oncolytic HSV-1 to express IpaH9.8 and found that the modified OV effectively antagonized GBP1, replicated to a higher titer in vitro and showed superior antitumor activity in vivo. Our study features a strategy for improving the replication of OVs via targeting a restriction factor and achieving promising therapeutic efficacy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncolytics Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncolytics Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos