Nondepleting anti-CD4 antibody treatment prolongs lung-directed E1-deleted adenovirus-mediated gene expression in rats

Human Gene Therapy
D LeiJ Kolls

Abstract

E1-deleted adenoviral vectors are efficient vectors for somatic cell gene therapy, but transgene expression is limited in part by a cytotoxic T cell response directed against virally transduced cells. Moreover, the development of a neutralizing antibody response limits secondary gene transfer with these vectors. Therapy with a depleting anti-CD4 antibody permits prolonged transgene expression in the lung and liver of mice. Furthermore, transient depletion of CD4+ lymphocytes blocks neutralizing antibody production and therefore allows repeat administration and expression of E1-deleted recombinant adenovirus. In this study, we investigated the efficacy of a novel nondepleting anti-CD4 antibody (RIB 5/2) in a model of lung-directed gene therapy in outbred rats. Treatment with RIB 5/2 permitted prolonged reporter gene expression and reduced adenovirus-induced peribronchial and alveolar inflammation in the lung. Moreover administration of RIB 5/2 blocked the development of an anti-adenoviral neutralizing antibody response in the lung and permitted secondary administration and expression of a recombinant adenovirus. These data support the role of immunomodulation in prolonging in vivo transgene expression by recombinant adenovirus.

References

Sep 1, 1995·Nature Medicine·C Wilson, M A Kay
Mar 27, 1994·Transplantation·J A PowelsonA B Cosimi
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·J F EngelhardtJ M Wilson
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y YangJ M Wilson
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·J KollsB Beutler
Jun 1, 1993·Current Opinion in Genetics & Development·K F Kozarsky, J M Wilson
Feb 1, 1996·The Journal of Infectious Diseases·J E ShellitoJ M Beck
Dec 1, 1995·The Journal of Clinical Investigation·J M Wilson

❮ Previous
Next ❯

Citations

Feb 11, 1999·Journal of Neuroscience Research·G M Smith, M I Romero
Oct 16, 2002·Biochemical and Biophysical Research Communications·Yan ChenKeith D K Luk
Feb 16, 2000·Journal of Neuroimmunology·K KajiwaraK J Wood
Nov 14, 1997·Current Opinion in Biotechnology·I KovesdiT J Wickham
Mar 24, 1999·Molecular Medicine Today·M A Morsy, C T Caskey
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Terence R FlotteJim Hu
Jan 1, 2010·Microbes and Environments·Takahiro SegawaShiro Kohshima
Mar 25, 2009·Journal of Clinical Biochemistry and Nutrition·Ji-Young HongMasayasu Inoue
Mar 27, 2010·The Journal of General and Applied Microbiology·Kazunari UshidaHiroshi Kanda
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·Z L JiangP R Clemens
May 14, 2005·Cancer Gene Therapy·Weitao HuangPaul Schwarzenberger
Apr 26, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P SchwarzenbergerJ K Kolls
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·P SchwarzenbergerJ K Kolls
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florencia McAllisterJay K Kolls
Jan 7, 2000·Biochemical and Biophysical Research Communications·Y OkuboS I Miyatake
Feb 24, 2001·The American Journal of the Medical Sciences·P SchwarzenbergerJ K Kolls

❮ Previous
Next ❯

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.