Abstract

Public Health Relevance

Although the first successful human gene therapy was performed in XSCID patients, the occurrence of T cell leukemia in four of ten successfully treated patients three to six years following treatment has shown that gene therapy is not without potential serious adverse side effects. In this application we will use the unique canine XSCID model as a pre-clinical large and long-lived animal model to test new vectors and strategies for improving the efficacy and durability of retroviral gene therapy prior to treating human patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI043745-11A2
Application #
7662912
Study Section
Transplantation, Tolerance, and Tumor Immunology (TTT)
Program Officer
Johnson, David R
Project Start
2009-06-05
Project End
2011-05-31
Budget Start
2009-06-05
Budget End
2010-05-31
Support Year
11
Fiscal Year
2009
Total Cost
$646,933
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Other Clinical Sciences
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Felsburg, Peter J; De Ravin, Suk See; Malech, Harry L et al. (2015) Gene therapy studies in a canine model of X-linked severe combined immunodeficiency. Hum Gene Ther Clin Dev 26:50-6
Luff, Jennifer A; Yuan, Hang; Kennedy, Douglas et al. (2014) Keratinocyte antiviral response to Poly(dA:dT) stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency. PLoS One 9:e102033
Kennedy, Douglas R; Hartnett, Brian J; Kennedy, Jeffrey S et al. (2011) Ex vivo ?-retroviral gene therapy of dogs with X-linked severe combined immunodeficiency and the development of a thymic T cell lymphoma. Vet Immunol Immunopathol 142:36-48
Kennedy, Douglas R; McLellan, Kyle; Moore, Peter F et al. (2009) Effect of ex vivo culture of CD34+ bone marrow cells on immune reconstitution of XSCID dogs following allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 15:662-70
Vernau, William; Hartnett, Brian J; Kennedy, Douglas R et al. (2007) T cell repertoire development in XSCID dogs following nonconditioned allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 13:1005-15
Suter, Steven E; Gouthro, Terry A; O'Malley, Thomas et al. (2007) Marking of peripheral T-lymphocytes by retroviral transduction and transplantation of CD34+ cells in a canine X-linked severe combined immunodeficiency model. Vet Immunol Immunopathol 117:183-96
Goldschmidt, Michael H; Kennedy, Jeffrey S; Kennedy, Douglas R et al. (2006) Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs. J Virol 80:6621-8
Swerdlow, Mathew P; Kennedy, Douglas R; Kennedy, Jeffrey S et al. (2006) Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells. Vet Immunol Immunopathol 114:313-9
Ting-De Ravin, Suk See; Kennedy, Douglas R; Naumann, Nora et al. (2006) Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy. Blood 107:3091-7
Suter, S E; Gouthro, T A; McSweeney, P A et al. (2006) Optimized transduction of canine paediatric CD34(+) cells using an MSCV-based bicistronic vector. Vet Res Commun 30:881-901

Showing the most recent 10 out of 19 publications