The Immune Function Studies Core (Core C) is designed to support the proposed studies of yc Foamy Virus gene therapy for SCID-Xl that will utilize in vitro testing in cell lines as well as in vivo testing using pre- clinical animal models. The Core will support all three projects (1, 2, and 3) of this Program Project Grant and is focused primarily on evaluation of functional immune recovery after gene therapy in this severe immunodeficiency disorder. The Core will perform multi-parameter flow cytometry analyses of human, mouse, and canine cells to measure viral marking and immune reconstitution after yc FV gene therapy. In addition. Core C will evaluate restoration of specific functional deficits (for example restoration of lL-2 signaling) in yc FV treated cells and will work with the SCRl Immunology Diagnostic Laboratory (IDL) to analyze functional immune responses to neoantigen (bacteriophage OX174) vaccination in treated dogs. Flow cytometry and gene sequencing will be performed by the Core to rapidly identify affected SCID-Xl dogs shortly after birth. Core C personnel will directly assist project investigators in the analysis and interpretation of data generated by the Core. Data from these analyses will be used to evaluate which yc FV vector is most efficacious and which conditioning regimen facilitates the most complete immune recovery.
Immune dysfunction and susceptibility to severe, life-threatening infections are the hallmarks of the fatal childhood immunodeficiency disorder, SCID-Xl. Evaluation of immune reconstitufion and recovery of functional immune responses after potentially curative gene therapy is therefore vital for judging whether a particular treatment is efficacious. Core C will evaluate immune recovery in this trial of Foamy Viral mediated gene therapy for SCID-Xl.
|Browning, D L; Everson, E M; Leap, D J et al. (2017) Evidence for the in vivo safety of insulated foamy viral vectors. Gene Ther 24:187-198|
|Singh, Swati; Khan, Iram; Khim, Socheath et al. (2017) Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector. Mol Ther Methods Clin Dev 4:1-16|
|Browning, Diana L; Trobridge, Grant D (2016) Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy. Biomedicines 4:|
|Browning, Diana L; Collins, Casey P; Hocum, Jonah D et al. (2016) Insulated Foamy Viral Vectors. Hum Gene Ther 27:255-66|
|Bii, Victor M; Trobridge, Grant D (2016) Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors. Cancers (Basel) 8:|
|Nalla, Arun K; Williams, Theodore F; Collins, Casey P et al. (2016) Lentiviral vector-mediated insertional mutagenesis screen identifies genes that influence androgen independent prostate cancer progression and predict clinical outcome. Mol Carcinog 55:1761-1771|
|Humbert, Olivier; Gisch, Don W; Wohlfahrt, Martin E et al. (2016) Development of Third-generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T-cells. Mol Ther 24:1237-46|
|Everson, Elizabeth M; Olzsko, Miles E; Leap, David J et al. (2016) A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance. Mol Ther Methods Clin Dev 3:16048|
|Hocum, Jonah D; Linde, Ian; Rae, Dustin T et al. (2016) Retargeted Foamy Virus Vectors Integrate Less Frequently Near Proto-oncogenes. Sci Rep 6:36610|
|Nalla, Arun K; Trobridge, Grant D (2016) Prospects for Foamy Viral Vector Anti-HIV Gene Therapy. Biomedicines 4:|
Showing the most recent 10 out of 39 publications