Expression of anti-VEGF antibody together with anti-EGFR or anti-FAP enhances tumor regression as a result of vaccinia virotherapy.
The tumor microenvironment plays an important role in tumor growth and progression. Here we demonstrate that vaccinia virus-mediated, constitutively expressed intratumoral antibodies against vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and fibroblast activation protein (FAP) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis, cell proliferation, and stromagenesis in virus-colonized tumors. In contrast to the tumor growth inhibition by the three tumor growth-inhibiting antibodies individually, when two of the three antibodies were expressed simultaneously by single vaccinia virus strains tumor regression was further enhanced. These findings strongly indicate that interference with the two tumor growth-stimulating mechanisms did in fact result in enhanced therapeutic efficacy in tumor xenograft models and may lead to an effective therapy in patients with cancer.
Department of Biochemistry, Rudolph Virchow Center for Experimental Biomedicine, Institute for Molecular Infection Biology, University of Würzburg , Würzburg, Germany.
Ting
T
Huang
Genelux Corporation, San Diego Science Center , San Diego, California, USA.
Huiqiang
H
Wang
Genelux Corporation, San Diego Science Center, San Diego, California, USA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, USA.
Nanhai G
NG
Chen
Genelux Corporation, San Diego Science Center , San Diego, California, USA.
Alexa
A
Frentzen
Genelux Corporation, San Diego Science Center, San Diego, California, USA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, USA; Division of Neurosurgery, University of California, San Diego, California, USA.
Boris
B
Minev
Department of Biochemistry, Rudolph Virchow Center for Experimental Biomedicine, Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany; Genelux Corporation, San Diego Science Center, San Diego, California, USA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, USA.
Aladar A
AA
Szalay