Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory

Brisbane, Australia

Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory

Brisbane, Australia

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Dasari V.,Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory | Schuessler A.,Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory | Smith C.,Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory | Wong Y.,Berghofer Center for Immunotherapy and Vaccine Development and Tumor Immunology Laboratory | And 14 more authors.
Molecular Therapy - Methods and Clinical Development | Year: 2016

Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP) as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as “off-the-shelf” therapeutics as well as autologous T-cell therapies for transplant patients. © 2016 Official journal of the American Society of Gene & Cell Therapy

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