Genetically engineered oncolytic Newcastle disease virus mediates cytolysis of prostate cancer stem like cells

Genetically engineered oncolytic Newcastle disease virus mediates cytolysis of prostate cancer... •We genetically engineered NDV to selectively replicate and kill CaP cells only in the presence of prostate specific antigen (PSA), a chymotrypsin like serine protease secreted in the prostate tumor microenvironment.•In order to test whether rNDV would also be able to target and lyse CaP-initiating cells, we characterized stem-like populations from an androgen receptor (AR) negative, androgen independent human DU145 cell line and primary tumor xenograft derived prostaspheres (XPS). XPS expressed embryonic stem cell markers, such as Nanog, CD44 and Nestin.•Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice.•PSA activated NDV could also undergo multicycle replication in xenograft derived prostaspheres. Virus yield in these spheres were comparable to that in cell line derived prostaspheres.•Prostate specific antigen (PSA) activated recombinant Newcastle Disease Virus (rNDV) was selectively cytotoxic to tumor derived DU145 prostaspheres. An effective concentration (EC50) of 0.11-0.14 multiplicity of infection was sufficient to cause prostasphere cell death in serum free culture.•PSA activated rNDV was efficient in inducing cell death of cells and prostaspheres derived from primary tumor xenografts ex-vivo, thus signifying a potential in vivo efficacy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Biotechnology Elsevier

Genetically engineered oncolytic Newcastle disease virus mediates cytolysis of prostate cancer stem like cells

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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier B.V.
ISSN
0168-1656
eISSN
1873-4863
D.O.I.
10.1016/j.jbiotec.2017.09.015
Publisher site
See Article on Publisher Site

Abstract

•We genetically engineered NDV to selectively replicate and kill CaP cells only in the presence of prostate specific antigen (PSA), a chymotrypsin like serine protease secreted in the prostate tumor microenvironment.•In order to test whether rNDV would also be able to target and lyse CaP-initiating cells, we characterized stem-like populations from an androgen receptor (AR) negative, androgen independent human DU145 cell line and primary tumor xenograft derived prostaspheres (XPS). XPS expressed embryonic stem cell markers, such as Nanog, CD44 and Nestin.•Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice.•PSA activated NDV could also undergo multicycle replication in xenograft derived prostaspheres. Virus yield in these spheres were comparable to that in cell line derived prostaspheres.•Prostate specific antigen (PSA) activated recombinant Newcastle Disease Virus (rNDV) was selectively cytotoxic to tumor derived DU145 prostaspheres. An effective concentration (EC50) of 0.11-0.14 multiplicity of infection was sufficient to cause prostasphere cell death in serum free culture.•PSA activated rNDV was efficient in inducing cell death of cells and prostaspheres derived from primary tumor xenografts ex-vivo, thus signifying a potential in vivo efficacy.

Journal

Journal of BiotechnologyElsevier

Published: Oct 20, 2017

References

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