TOA02, a recombinant adenovirus with tumor-specific granulocyte macrophage colony-stimulating factor expression, has limited biodistribution and low toxicity in rhesus monkeys

Human Gene Therapy Methods
Ling WangFu-bing Shen

Abstract

TOA02 is a genetically modified oncolytic adenovirus that contains human granulocyte macrophage colony-stimulating factor (hGM-CSF). It has been verified in vitro that TOA02 can specifically replicate in tumor cells that possess high telomerase reverse transcriptase activity and Rb pathway deficiency. However, the replication specificity, hGM-CSF expression, and toxicity of TOA02 in vivo are still unknown. Therefore, the biosafety of TOA02 remains a critical issue before its potential clinical use. In this study, viral replication and hGM-CSF expression levels were investigated in both xenograft nude mouse models and rhesus monkeys, and chronic toxicity was evaluated in rhesus monkeys. Our results show that (1) the replication and hGM-CSF expression of TOA02 are high in tumor model, (2) there are no hGM-CSF expression and continuous viral replication in rhesus monkeys except in pancreas and epididymis, and (3) the antiadenovirus antibody was positive in the chronic toxicity experiment, but pathological change of blood cytology and blood biochemistry were not found. There were no other histopathology lesions apart from skin inflammation of the administration region, lymphadenitis of draining lymph nodes. Our findings suggest tha...Continue Reading

References

May 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J A ThompsonA Fefer
Sep 17, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lixin ZhangAlbert Deisseroth
Feb 12, 2004·Journal of Medical Ethics·S J L EdwardsR Huxtable
Jul 10, 2004·Journal of Cancer Research and Clinical Oncology·C-Q SuQ-J Qian
Jan 25, 2005·Bioorganic & Medicinal Chemistry Letters·Mitsuko MaedaKoichi Kawasaki
May 17, 2007·Current Cancer Drug Targets·Youssef JounaidiDavid J Waxman
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ziv GilRichard J Wong
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Chien-Kuo Tai, Noriyuki Kasahara
Feb 7, 2009·Cancer Gene Therapy·J J Cody, J T Douglas
Apr 9, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Oh-Joon KwonChae-Ok Yun

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
density gradient centrifugation
PCR
xenograft
ELISA

Software Mentioned

SPSS19

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.