Absence of in vitro or in vivo bystander effects in a thymidine kinase-transduced murine T lymphoma.
Among the goals of an optimal gene transfer system are a predictably high efficiency of transfer and the ability to confer stable gene expression. An additional benefit of strategies designed to target tumor or effector cells could be the induction of a bystander effect. Although tumor killing by the bystander effect in vivo has been obtained in several types of malignant tumors, it has not been reported for T lymphomas. The goals of this work were to determine the stability of the expression of the herpes simplex virus type-1 thymidine kinase and the low-affinity receptor for nerve growth factor truncated of its intracellular domain (deltaLNGFR) genes inserted in a murine T lymphoma; in addition, we sought to determine whether a bystander effect (direct or indirect) was present after treatment of the transduced tumor with ganciclovir. This study demonstrates a high level of stable expression of both genes in the T lymphoma in vitro and in vivo. However, we could not detect direct or indirect bystander effects in vivo mediated by the herpes simplex virus thymidine kinase/ganciclovir system in this tumor of lymphocyte origin. This is the first report to investigate bystander effects in vivo on a T-cell lineage tumor; in addition, this report has implications for the therapeutic transfer of non-transformed, antigen-specific T cells in vivo.
Rivas
C
C
Department of Haematology, Imperial College of Science, Technology, and Medicine, Hammersmith Hospital, London, United Kingdom.
Chandler
P
P
Melo
J V
JV
Simpson
E
E
Apperley
J F
JF
D000818:Animals; D015139:Blotting, Southern; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D007279:Injections, Subcutaneous; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000235:genetics; D016133:Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014161:Transduction, Genetic
D017931:DNA Primers; D020932:Nerve Growth Factor; D013937:Thymidine Kinase; D015774:Ganciclovir