Preclinical studies on suicide gene therapy for head/neck cancer: a novel method for evaluation of treatment efficacy.
BACKGROUND
Malignancies of the oral cavity and oropharynx account for 31% of all diagnosed cancers in India. In most cases, patients present with tumours that are clinically stage III/IV where surgery, radiotherapy and chemotherapy have not been very effective. Hence, there is an urgent need for alternate treatment modalities. Gene therapy is a recent development shown to be effective in various malignancies. In this study we have attempted to cause bulk reduction in tumour volume using the HSVtk/ganciclovir strategy, solely on the basis of the 'bystander' effect.


METHODS
Nude mouse xenograft tumours of human head/neck cancer were engrafted with cells expressing viral thymidine kinase. After treatment with 8 mM ganciclovir for 14 days, the treatment efficacy was monitored. A novel method has been devised to evaluate cell kill microscopically in the whole tumour.


RESULTS
Of the 11 mice included in the study, 9 showed a significant reduction in total tumour volume of treated versus control tumours (p = 0.015).


CONCLUSIONS
Bulk reduction in tumour load can be brought about without use of viral vectors for gene transfer solely by the bystander effect.
Thomas
S M
SM
Genetic Engineering Unit, Tata Memorial Hospital, Tata Memorial Center, Parel, Mumbai, India.
Naresh
K N
KN
Wagle
A S
AS
Mulherkar
R
R
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics*; D014162:Transfection; D014183:Transplantation, Heterologous
D000998:Antiviral Agents; D011994:Recombinant Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir