Biodistribution and safety of intravenously administered oncolytic Newcastle disease virus
LIU Man
LI Wenliang
FENG Lanting
LI Qian
WEI Ding
BIAN Huijie
Abstract：Objective To evaluate the safety and in vivo distribution of oncolytic viruses administered intravenously.Methods The velogenic strain Newcastle disease virus(NDV)Italien was used to systematically assess its safety and biodistribution after intravenous injection in immunocompetent BALB/c mice.Mice were randomly divided into four groups:control group(PBS),low-dose group(5 × 108 PFU),medium-dose group(1 × 109 PFU),and high-dose group(5 × 109 PFU),each receiving a single tail vein injection.Acute toxicity was evaluated by observing general condition,body mass changes,mortality,and histopathology(HE staining).qRT-PCR was used to detect viral genome copy numbers in the heart,liver,spleen,lung,kidney,and plasma at different time points(1h,6 h,1d,3 d,7 d)after a single injection(5 × 108 PFU)and after multiple injections(5 × 107 PFU per injection,once every 3 d for a total of 3 injections).Pharmacokinetic parameters were calculated.Additionally,an rNDV-Luci(recombinant virus expressing luciferase)group was established to observe viral replication dynamics in vivo(at 24 h and 72 h)using small animal in vivo imaging.Results After a single intravenous injection of NDV Italien,the no-observed-adverse-effect level was 1 × I 09 PFU,which was 100 times the effective therapeutic dose.All mice in the low-dose(5 × 108 PFU)and medium-dose(1 × 109 PFU)groups survived,showing only transient body mass loss and mild histopathological changes.Mice in the high-dose group(5 × 109 PFU)all died within 48 h,presenting severe injuries including diffuse pulmonary hemorrhage and focal hepatic necrosis.Quantitative viral genome analysis showed that the lung was the primary target organ for viral distribution,reaching peak levels at 6 h post-injection followed by rapid clearance.Viral loads in the liver,spleen,and other organs were lower and exhibited a monophasic clearance pattern.In vivo imaging further confirmed that viral replication was transient and mainly localized in the lung,being largely cleared within 72 h.Multiple injections did not lead to viral accumulation in plasma or tissues,with the spleen demonstrating the most prominent clearance capacity.Conclusion Intravenous administration of NDV Italien strain is well tolerated within the therapeutic dose range in immunocompetent mice,although a dose of 5 × 109 PFU can cause lung and liver injuries.The lung is the primary target organ,suggesting a potential therapeutic advantage for pulmonary tumors.This study provides important safety evidence for the clinical translation of recombinant velogenic NDV.
Keywords：oncolytic virusNewcastle disease virusintravenous injectionbiodistributionsafetytumor biotherapytumor immunotherapyoncolytic virotherapy
Publication Date：2026-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 953-960 )