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Updated: Jul 8, 2026
Rescue of Recombinant Newcastle Disease Virus from cDNA
Published on: October 11, 2013
Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two
F Pühler1, J Willuda, J Puhlmann
1Therapeutic Research Group Oncology, Bayer Schering Pharma AG, Berlin, Germany.
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-antigen in tumor tissue. This approach will allow to combine the advantages of oncolytic RNA viruses and monoclonal antibodies in a single powerful anticancer agent with improved or even new therapeutic properties.
Insights
Genetically engineered Newcastle disease virus (NDV) can deliver therapeutic monoclonal antibodies directly to tumor cells. This novel approach combines oncolytic virus therapy with antibody treatment for enhanced cancer fighting capabilities.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Molecular virology
Background:
- Wild-type mesogenic Newcastle disease virus (NDV) strains exhibit natural oncolytic activity, selectively targeting tumor cells.
- Current clinical trials utilize these wild-type NDV strains for cancer treatment.
- No prior studies have explored genetically engineered mesogenic NDV for enhanced oncolytic effects.
Purpose of the Study:
- To generate recombinant mesogenic NDV (MTH68 strain) with enhanced therapeutic potential.
- To assess the feasibility of inserting multiple transgenes into the NDV genome without compromising viral function.
- To engineer NDV to express functional monoclonal antibodies for targeted cancer therapy.
Main Methods:
- Generation of recombinant NDV MTH68 strain.
- Insertion of transgenes encoding monoclonal antibody heavy and light chains into the viral genome.
- Evaluation of viral growth, oncolytic potency, and tumor-selective replication.
- Assessment of antibody production and functionality in infected tumor cells.
Main Results:
- Successfully generated recombinant NDV capable of accommodating up to two additional transgenes (25 and 50 kDa).
- Transgene insertion did not impair viral growth, oncolytic activity, or tumor-specific replication.
- Recombinant NDV efficiently produced and secreted functional full-size IgG monoclonal antibodies.
- These antibodies specifically bound to target antigens within tumor tissue.
Conclusions:
- Genetically engineered mesogenic NDV can serve as a platform for delivering therapeutic monoclonal antibodies directly to tumors.
- This dual-action approach combines oncolytic virotherapy with antibody-based therapy in a single agent.
- This strategy holds promise for developing novel, potent anticancer therapeutics with improved efficacy.
