Recombinant Newcastle disease virus as a vaccine vector for cancer therapy.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Adam VigilAdolfo García-Sastre

Abstract

Naturally occurring strains of Newcastle disease virus (NDV) are currently being investigated in multiple clinical trials for oncolytic cancer therapy in the United States and abroad. We have previously reported, for the first time, the development of recombinant NDVs designed for enhanced cancer therapeutic efficacy. Specifically, we have shown that NDV engineered to express interleukin-2 (IL-2) generates a robust therapeutic response associated with increased tumor-specific T-cell infiltration after intratumoral administration in mice. We have now demonstrated that this therapeutic response is dependent on T cells and we have investigated the potential to focus the NDV-induced immune response toward a tumor-associated antigen (TAA) to enhance the inherent therapeutic efficacy of NDV further. We found that intratumoral treatments of tumor-bearing mice with recombinant NDV expressing a model TAA elicited an enhanced tumor-specific response, resulting in a significant increase in the number of complete tumor regressions compared with control NDV. Additionally, coadministration of NDV expressing a model TAA with NDV expressing IL-2 enhanced the TAA-directed response and led to more complete tumor regressions. Our results show tha...Continue Reading

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Citations

Jan 26, 2011·Immunology and Cell Biology·Lawrence W LeungChristopher F Basler
Feb 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dmitriy ZamarinYuman Fong
Dec 2, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Paul T SobolKaren L Mossman
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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
fluorescence-activated cell-sorting
reverse transcription PCR
flow cytometry

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