Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes

Gene Therapy
F PühlerR Beier

Abstract

The most advanced oncolytic Newcastle disease virus (NDV) strains that are used in clinical trials for the treatment of cancer are wild-type mesogenic strains. These virus strains have an inherent, nongenetically engineered, oncolytic activity and selectively replicate in tumor cells but not in normal human cells. To date no investigations have been performed with genetically engineered mesogenic NDV regarding the oncolytic activity. We describe here the generation of recombinant viruses of the mesogenic naturally oncolytic NDV strain MTH68. We show that not only one, but also two additional transgenes coding for amino-acid chains with a molecular weight of 25 and 50 kDa can be inserted into the viral genome without affecting viral growth, oncolytic potency or tumor-selective replication of the virus. Transgenic expression of the heavy and light chains of a monoclonal antibody, as separate additional transcriptional cassettes, leads to the expression of full immunoglobulin G (IgG) monoclonal antibody by recombinant NDV. Infection of tumor cells with antibody-transgenic viruses results in the efficient production and secretion of a functional full size IgG antibody by the tumor cells, that specifically binds to its target-antige...Continue Reading

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Citations

Feb 24, 2012·Gene Therapy·R BeierD Mumberg
Jan 4, 2012·Clinical and Experimental Pharmacology & Physiology·Lixiang Zhao, Haiyan Liu
Mar 8, 2012·Future Microbiology·Dmitriy Zamarin, Peter Palese
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Feb 23, 2020·Human Vaccines & Immunotherapeutics·Moumita MondalDongming Zhou
Apr 23, 2020·Viruses·Muhammad Bashir BelloAbdul Rahman Omar

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