In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies.
Abstract: Lentiviral-based vectors hold great promise as gene delivery vehicles for the treatment of a wide variety of diseases. We have previously reported the development of a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), which is able to efficiently transduce dividing and nondividing cells both in vitro and in vivo. Here, we report on the application of EIAV vectors for the systemic delivery of an antibody fusion protein designed for the treatment of cancer. The therapeutic potential of a single chain antibody against the tumour-associated antigen, 5T4, fused to immune enhancer moieties has been demonstrated in vitro and here we evaluate the genetic delivery of a 5T4 scFv fused to B7.1 (scFvB7) using an EIAV vector. The kinetics and concentration of protein produced following both intravenous (i.v.) and intramuscular (i.m.) administration was determined in immune competent adult mice. In addition, the immune response to the EIAV vector and the transgene were determined. Here, we show that a single injection of EIAV expressing scFv-B7 can give rise to concentrations of protein in the range of 1-5 microg/ml that persist in the sera for more than 50 days. After a second injection, concentrations of scFv-B7.1 rose as high as 20 microg/ml and levels greater than 2 microg/ml were present in the sera of all mice injected i.v. after 210 days despite the detection of antibodies against both the transgene and viral envelope for the duration of this study. These results demonstrate the potential of EIAV as a gene therapy vector for long-term production of therapeutic recombinant proteins.
Publication Date: 2005-03-18 PubMed ID: 15772687DOI: 10.1038/sj.gt.3302484Google Scholar: Lookup
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- Journal Article
Summary
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The study explores the potential of using equine infectious anaemia virus (EIAV) based vectors in gene therapy to generate therapeutic antibodies for cancer treatment. Researchers found that the EIAV vector produced and maintained therapeutic recombinant protein levels in mice for an extended period.
Study Objective and Methodology
- The main goal of the research was to investigate the potential of Lentiviral-based vectors, specifically a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), to transduce (introduce genes into) cells both in vitro (outside a living organism) and in vivo (within a living organism).
- The researchers leveraged the EIAV vectors for the systemic delivery of an antibody fusion protein, specifically targeting the treatment of cancer.
- This antibody fusion protein is a single chain antibody against the tumor-associated antigen, 5T4, fused with immune enhancer moieties.
- The effectiveness of this combination had been demonstrated in vitro, and this study was designed to evaluate the genetic delivery of a 5T4 scFv fused to B7.1 (scFvB7) using an EIAV vector in a living organism.
- The concentration and kinetics of the protein produced following both intravenous (i.v.) and intramuscular (i.m.) administrations were measured in immune competent adult mice. In addition, the researchers also studied the immune response to the EIAV vector and the transgene.
Study Findings
- They observed that a single injection of EIAV expressing scFv-B7 led to protein concentrations in the range of 1-5 micrograms per milliliter in the mice’s serum, and these levels remained persistent for over 50 days.
- Following a second injection, the concentrations of scFv-B7.1 rose as high as 20 micrograms per milliliter, and levels greater than 2 micrograms per milliliter were present in the sera of all mice that were injected intravenously.
- This was observed even after 210 days and despite the detection of antibodies against both the transgene and the viral envelope throughout the study.
Conclusions
- The results of this study demonstrate the potential of EIAV as a gene therapy vector for the long-term production of therapeutic recombinant proteins.
- This could pave the way for the development of more efficient and persistent treatment strategies for cancer and potentially other diseases.
Cite This Article
APA
Lamikanra A, Myers KA, Ferris N, Mitrophanous KA, Carroll MW.
(2005).
In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies.
Gene Ther, 12(12), 988-998.
https://doi.org/10.1038/sj.gt.3302484 Publication
Researcher Affiliations
- Oxford BioMedica, Medawar Building, Robert Robinson Avenue, Oxford Science Park, UK.
MeSH Terms
- Animals
- Antibodies / blood
- B7-1 Antigen / genetics
- Cell Line, Tumor
- Enzyme-Linked Immunosorbent Assay / methods
- Female
- Flow Cytometry
- Gene Expression
- Genetic Therapy / methods
- Genetic Vectors / administration & dosage
- Green Fluorescent Proteins / genetics
- Immunoglobulin Fc Fragments / genetics
- Immunoglobulin Fc Fragments / immunology
- Inducible T-Cell Co-Stimulator Ligand
- Infectious Anemia Virus, Equine / genetics
- Injections, Intramuscular
- Injections, Intravenous
- Membrane Glycoproteins / genetics
- Membrane Glycoproteins / immunology
- Mice
- Mice, Inbred BALB C
- Neoplasms / immunology
- Neoplasms / metabolism
- Neoplasms / therapy
- Polymerase Chain Reaction / methods
- Recombinant Fusion Proteins / blood
- Recombinant Fusion Proteins / genetics
- Recombinant Fusion Proteins / immunology
- Time Factors
- Transduction, Genetic / methods
- Viral Envelope Proteins / immunology
Citations
This article has been cited 2 times.- Fallah A, Estiri H, Parrish E, Soleimani M, Zeinali S, Zadeh-Vakili A. Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy.. Cell J 2020 Jan;21(4):433-443.
- Cockrell AS, Kafri T. Gene delivery by lentivirus vectors.. Mol Biotechnol 2007 Jul;36(3):184-204.
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