Pregled bibliografske jedinice broj: 1187886
Development of a low-seroprevalence, αvβ6 integrin-selective virotherapy based on human adenovirus type 10
Development of a low-seroprevalence, αvβ6 integrin-selective virotherapy based on human adenovirus type 10 // Molecular Therapy - Oncolytics, 25 (2022), 43-56 doi:10.1016/j.omto.2022.03.007 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 1187886 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Development of a low-seroprevalence, αvβ6
integrin-selective virotherapy based on human
adenovirus type 10
Autori
Bates, Emily A. ; Davies, James A. ; Vanova, Jana ; Nestić, Davor ; Meniel, Valerie S ; Koushyar, Sarah ; Cunliffe, Tabitha G. ; Mundy, Rosie M. ; Moses, Elise ; Uusi-Kerttula, Hanni K. ; Baker, Alexander T. ; Cole, David K. ; Majhen, Dragomira ; Rizkallah, Pierre J. ; Phesse, Toby ; Chester, John D ; Parker, Alan L.
Izvornik
Molecular Therapy - Oncolytics (2372-7705) 25
(2022);
43-56
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
oncolytic ; virotherapy ; adenovirus targeting ; αvβ6 integrin ; low seroprevalence ; structure
Sažetak
Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre- existing immunity will be beneficial for future clinical translation. We generated a low- seroprevalence HAdV-D10 serotype vector incorporating an αvβ6 integrin-selective peptide, A20, to target αvβ6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating “off-target” hepatic sequestration in vivo. We engineered an A20 peptide that selectively binds αvβ6 integrin into the DG loop of HAdV-D10 fiber knob. Assays in αvβ6+ cancer cell lines demonstrated significantly increased transduction mediated by αvβ6-targeted variants compared with controls, confirmed microscopically. HAdV-D10.A20 resisted neutralization by neutralizing HAdV-C5 sera. Systemic delivery of HAdV-D10.A20 resulted in significantly increased GFP expression in BT20 tumors. Replication-competent HAdV-D10.A20 demonstrated αvβ6 integrin-selective cell killing in vitro and in vivo. HAdV-D10 possesses characteristics of a promising virotherapy, combining low seroprevalence, weak receptor interactions, and reduced off-target uptake. Incorporation of an αvβ6 integrin-selective peptide resulted in HAdV-D10.A20, with significant potential for clinical translation.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti
POVEZANOST RADA
Projekti:
HRZZ-IP-2019-04-6048 - Endocitoza adenovirusa i urođeni imunosni odgovor (AdenoIN) (Majhen, Dragomira, HRZZ - 2019-04) ( CroRIS)
Ustanove:
Institut "Ruđer Bošković", Zagreb
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus