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Simultaneous Insertion of Two Ligands in gD for Cultivation of Oncolytic Herpes Simplex Viruses in Noncancer Cells and Retargeting to Cancer Receptors

Published on Dec 20, 2017in Journal of Virology4.324
路 DOI :10.1128/jvi.02132-17
Valerio Leoni8
Estimated H-index: 8
(UNIBO: University of Bologna),
Biljana Petrovic5
Estimated H-index: 5
(UNIBO: University of Bologna)
+ 2 AuthorsGabriella Campadelli-Fiume41
Estimated H-index: 41
(UNIBO: University of Bologna)
Abstract
  • References (49)
  • Citations (1)
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References49
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#1Ekaterina E. Heldwein (Harvard University)H-Index: 23
#2Huan Lou (UPenn: University of Pennsylvania)H-Index: 27
Last. Stephen C. Harrison (Harvard University)H-Index: 109
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Glycoprotein B (gB) is the most conserved component of the complex cell-entry machinery of herpes viruses. A crystal structure of the gB ectodomain from herpes simplex virus type 1 reveals a multidomain trimer with unexpected homology to glycoprotein G from vesicular stomatitis virus (VSV G). An 伪-helical coiled-coil core relates gB to class I viral membrane fusion glycoproteins; two extended 尾 hairpins with hydrophobic tips, homologous to fusion peptides in VSV G, relate gB to class II fusion p...
415 CitationsSource
#1Chantal G Lemay (Ottawa Hospital Research Institute)H-Index: 10
#2Brian A. Keller (Ottawa Hospital Research Institute)H-Index: 1
Last. John C. Bell (Ottawa Hospital Research Institute)H-Index: 63
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Abstract Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. A full arsenal of selective, safe, and effective viruses has been developed with some emerging pre-clinical research focusing on optimizing these therapies in the face of remaining challenges, both in the bloodstream and in the tumour microenvironment. Herein we discuss the recent progress in pre-clinical virotherapy research to address these challenges, wi...
5 CitationsSource
#1Biljana PetrovicH-Index: 5
#2Valerio LeoniH-Index: 8
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3 CitationsSource
#1Brian Hutzen (Nationwide Children's Hospital)H-Index: 5
#2Chun-Yu Chen (Nationwide Children's Hospital)H-Index: 7
Last. Timothy P. Cripe (Nationwide Children's Hospital)H-Index: 30
view all 9 authors...
Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction of an anti-tumor immune response. Host-virus interactions are complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit the effectiveness of cancer immunotherapies. In an effort to improve this aspect of oncolytic virotherapy, we combined the oncolytic herpes virus HSV1716 with the transforming growth factor beta receptor 1 (TGF-尾R1) inhibitor A8301 to t...
14 CitationsSource
#1Achim K. Moesta (Amgen)H-Index: 14
#2Keegan Cooke (Amgen)H-Index: 11
Last. Pedro J. Beltran (Amgen)H-Index: 11
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Purpose: Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus, we characterized local and systemic antitumor immune responses driving efficacy in murine syngeneic models. Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEXmGM-CSF (talimogene laherparepvec with the mouse granulocyte-macropha...
24 CitationsSource
#1Karthik Sathiyamoorthy (Stanford University)H-Index: 9
#2Jia Chen (NU: Northwestern University)H-Index: 11
Last. Theodore S. Jardetzky (Stanford University)H-Index: 51
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Enveloped viruses have evolved diverse transmembrane proteins and protein complexes to enable host cell entry by regulating and activating membrane fusion in a target cell-specific manner. In general terms, the entry process requires a receptor binding step, an activation step and a membrane fusion step, which can be encoded within a single viral protein or distributed among multiple viral proteins. HIV and influenza virus, for example, encode all of these functions in a single trimeric glycopro...
25 CitationsSource
#1Valerio Leoni (UNIBO: University of Bologna)H-Index: 8
#2Valentina Gatta (UNIBO: University of Bologna)H-Index: 4
Last. Gabriella Campadelli-Fiume (UNIBO: University of Bologna)H-Index: 41
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7 CitationsSource
#1Biljana Petrovic (UNIBO: University of Bologna)H-Index: 5
#2Tatiana Gianni (UNIBO: University of Bologna)H-Index: 15
Last. Gabriella Campadelli-Fiume (UNIBO: University of Bologna)H-Index: 41
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15 CitationsSource
#1William F. Goins (University of Pittsburgh)H-Index: 35
#2Bonnie Hall (University of Pittsburgh)H-Index: 2
Last. Joseph C. Glorioso (University of Pittsburgh)H-Index: 63
view all 4 authors...
Gene therapy applications depend on vector delivery and gene expression in the appropriate target cell. Vector infection relies on the distribution of natural virus receptors that may either not be present on the desired target cell or distributed in a manner to give off-target gene expression. Some viruses display a very limited host range, while others, including herpes simplex virus (HSV), can infect almost every cell within the human body. It is often an advantage to retarget virus infectivi...
6 CitationsSource
#1Guowei Gu (BCM: Baylor College of Medicine)H-Index: 12
#2Derek Dustin (BCM: Baylor College of Medicine)H-Index: 3
Last. Suzanne A.W. Fuqua (Baylor University)H-Index: 2
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In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown sever...
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#1Valerio Leoni (UNIBO: University of Bologna)H-Index: 8
#2Andrea Vannini (UNIBO: University of Bologna)H-Index: 7
Last. Gabriella Campadelli-Fiume (UNIBO: University of Bologna)H-Index: 41
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Oncolytic herpes simplex viruses (oHSVs) showed efficacy in clinical trials and practice. Most of them gain cancer-specificity from deletions/mutations in genes that counteract the host response, and grow selectively in cancer cells defective in anti-viral response. Because of the deletions/mutations, they are frequently attenuated or over-attenuated. We developed next-generation oHSVs, which carry no deletion/mutation, gain cancer-specificity from specific retargeting to tumor cell receptors鈥攅....
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#1Laura Menotti (UNIBO: University of Bologna)H-Index: 17
#2Elisa Avitabile (UNIBO: University of Bologna)H-Index: 21
Last. Gabriella Campadelli-Fiume (UNIBO: University of Bologna)H-Index: 41
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Previously, we engineered oncolytic herpes simplex viruses (o-HSVs) retargeted to the HER2 (epidermal growth factor receptor 2) tumor cell specific receptor by the insertion of a single chain antibody (scFv) to HER2 in gD, gH, or gB. Here, the insertion of scFvs to three additional cancer targets鈥擡GFR (epidermal growth factor receptor), EGFRvIII, and PSMA (prostate specific membrane antigen)鈥攊n gD 螖6鈥38 enabled the generation of specifically retargeted o-HSVs. Viable recombinants resulted from t...
5 CitationsSource
#1Xiao-Qin Liu (Yangtze University)H-Index: 1
#2Hong-Yi XinH-Index: 1
Last. Hong-Wu Xin (Yangtze University)H-Index: 1
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Oncolytic herpes simplex viruses (oHSVs) have been approved for clinical usage and become more and more popular for tumor virotherapy. However, there are still many issues for the oHSVs used in clinics and clinical trials. The main issues are the limited anti-tumor effects, intratumor injection, and some side effects. To overcome such challenges, here we review the genetic engineering of the envelope glycoproteins for oHSVs to target tumors specifically, and at the same time we summarize the man...
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#1Biljana PetrovicH-Index: 5
#2Valerio LeoniH-Index: 8
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