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Homing and survival of thymidine kinase-transduced human T cells in NOD/SCID mice.

Authors :
Di Ianni, Mauro
Terenzi, Adelmo
Falzetti, Franca
Bartoli, Andrea
Di Florio, Sabrina
Benedetti, Roberta
Venditti, Gigliola
Alfonsi, Diego
De Ioanni, Mariangela
Falini, Brunangelo
Tabilio, Antonio
Source :
Cancer Gene Therapy. Sep2002, Vol. 9 Issue 9, p756. 6p.
Publication Year :
2002

Abstract

The herpes simplex virus thymidine kinase (HSV-tk) gene conferring ganciclovir (GCV)-specific sensitivity to transduced cells might control Graft-versus-Leukemia (GvL)/Graft-versus-Host Disease (GvHD). Human T lymphocytes were engineered with an LSN-tk retroviral vector encoding tk and neomycin resistance (NeoR) genes. A total of 80×106 tk+ lymphocytes were injected intraperitoneally in NOD-SCID mice. Engraftment was evaluated by human CD45+/CD3+ cytofluorimetric analysis and NeoR-based polymerase chain reaction (PCR) on peripheral blood, bone marrow, liver, thymus, and spleen on day +5. After 14 days, GCV (10 mg/kg daily) cytofluorimetric analysis and PCR were repeated (day +19). Immunohistological studies with anti-CD3 monoclonal antibody followed by alkaline phosphatase and monoclonal anti–alkaline phosphatase staining were performed on spleen and liver at the same time points. Human CD45+/CD3+ cells were engrafted in all tissues on day +5 according to cytofluorimetry, immunohistology, and PCR. Lymphocytes “homed” to the white pulp T-cell area and to the red pulp; liver localization is prevalently at the periportal area. After GCV (day +19), cytofluorimetry and immunohistology showed very few CD3+ cells. PCR identified the transgene in 22% tissue samples (positive only in thymus and spleen). GvHD did not occur in any animal. These data demonstrate elevated doses of human-transduced CD3+ cells engraft in NOD/SCID mice; after GCV, very few CD3+ cells can be detected and those that escape treatment can be found in the thymus and in the spleen on day +19. Lack of full response to GCV may account for cases of GvHD in patients receiving tk-transduced T lymphocytes. Cancer Gene Therapy (2002) 9, 756–761 doi:10.1038/sj.cgt.7700495 [ABSTRACT FROM AUTHOR]

Subjects

Subjects :
*THYMIDINE
*T cells

Details

Language :
English
ISSN :
09291903
Volume :
9
Issue :
9
Database :
Academic Search Index
Journal :
Cancer Gene Therapy
Publication Type :
Academic Journal
Accession number :
8822781
Full Text :
https://doi.org/10.1038/sj.cgt.7700495