Abstract

We have focused our efforts on the use of lentiviral vectors to transfer genes to the rapamycin-resistant T cells. Using this approach, the majority of T cells in a given culture can be induced to express the new gene. We have also developed animal models to test the in vivo effect of these immuno-gene therapy strategies. Such models incorporate tumors and also evaluate graft-versus-host disease, which remains the main complication after allogeneic hematopoietic stem cell transplantation. To facilitate implementation of this project, we have entered into a cooperative research agreement with Lentigen Corporation to develop clinical protocols focusing on lentiviral delivery of suicide genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011219-02
Application #
8157710
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2010
Total Cost
$357,257
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Wang, James C M; Felizardo, Tânia C; Au, Bryan C Y et al. (2013) Engineering lentiviral vectors for modulation of dendritic cell apoptotic pathways. Virol J 10:240
Scaife, M; Pacienza, N; Au, B C Y et al. (2013) Engineered human Tmpk fused with truncated cell-surface markers: versatile cell-fate control safety cassettes. Gene Ther 20:24-34
Felizardo, Tania C; Foley, Jason; Steed, Kevin et al. (2013) Harnessing autophagy for cell fate control gene therapy. Autophagy 9:1069-79
Neschadim, Anton; Wang, James C M; Sato, Takeya et al. (2012) Cell fate control gene therapy based on engineered variants of human deoxycytidine kinase. Mol Ther 20:1002-13
Felizardo, T C; Wang, J C M; McGray, R A J et al. (2011) Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model. Gene Ther 18:986-95
Amarnath, Shoba; Mangus, Courtney W; Wang, James C M et al. (2011) The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med 3:111ra120
Symes, J C; Siatskas, C; Fowler, D H et al. (2009) Retrovirally transduced murine T lymphocytes expressing FasL mediate effective killing of prostate cancer cells. Cancer Gene Ther 16:439-52
Scaife, Matthew D; Neschadim, Anton; Fowler, D H et al. (2009) Novel application of lentiviral vectors towards treatment of graft-versus-host disease. Expert Opin Biol Ther 9:749-61
Loisel-Meyer, Severine; Felizardo, Tania; Mariotti, Jacopo et al. (2009) Potent induction of B- and T-cell immunity against human carcinoembryonic antigen-expressing tumors in human carcinoembryonic antigen transgenic mice mediated by direct lentivector injection. Mol Cancer Ther 8:692-702
Mossoba, Miriam E; Walia, Jagdeep S; Rasaiah, Vanessa I et al. (2008) Tumor protection following vaccination with low doses of lentivirally transduced DCs expressing the self-antigen erbB2. Mol Ther 16:607-17