Induction of anti-tumour immunity by suicide-gene-modified HPV-16-transformed hamster cells.
From K3/II, which is a highly oncogenic HPV16-transformed Syrian hamster cell line, thymidine-kinase(TK)-less cells, denoted B 49, were derived. B49 cells were transfected by a plasmid containing the herpes-simplex-virus TK gene (HSV TK) and several sub-lines expressing this gene were isolated from the transfected cultures. The HSV TK+ cells were highly sensitive to ganciclovir (GCV) and other anti-viral substances whose inhibitory effect is based on their phosphorylation by HSV TK. One of the cell lines, denoted KL1/6, exhibited relatively high stability of the HSV TK+ phenotype and was used in subsequent experiments. When KL1/6 cells were co-cultivated in the presence of GCV with various other cell lines of hamster, mouse or monkey origin, the by-stander effect (BE) was observed. GCV treatment of hamsters prevented development of tumours after the administration of KL1/6 cells but not K3/II cells. The treatment of animals with already established KL1/6-induced tumours resulted in tumour regression in all instances, but complete regression was observed only in animals carrying small tumours. The BE of KL1/6 cells on K3/II cells was also seen in vivo. In addition, concomitant immunity was observed in animals simultaneously inoculated with KL1/6 cells and K3/11 cells at 2 separate sites of the body. This effect was evident not only in animals in which KL1/6 tumours developed, but also in those in which tumour outgrowth was prevented by GCV treatment. In other experiments it was demonstrated that one KL1/6 + GCV treatment resulted in partial resistance, 2 such treatments in complete resistance to the challenge with K3/II cells.
Vonka
V
V
Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. vonka@hema.uhkt.anet.cz
Sobotková
E
E
Hamsíková
E
E
Smahel
M
M
Zák
R
R
Kitasato
H
H
Sainerová
H
H
D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000627:therapeutic use / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D015774:Ganciclovir / Q000627:therapeutic use / Q000633:toxicity; D011905:Genes, ras; D006801:Humans; D007668:Kidney; D008647:Mesocricetus; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D016366:Open Reading Frames; D027383:Papillomaviridae / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D016662:Virus Integration
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir