Immunization with live HPV-16-transformed mouse cells expressing the herpes simplex thymidine kinase and either GM-CSF or IL-2.
From mouse (C57BL/6) HPV-16 transformed cells denoted MK16/1/IIIABC (MK16) a cellular thymidine kinase deficient (cTK-) cell line was isolated. These cTK- cells were transduced by bicistronic recombinant adeno-associated viruses (rAAV) carrying the herpes simplex virus thymidine kinase gene and the gene for either the mouse granulocyte-macrophage colony stimulating factor (GM-CSF) or mouse interleukin-2 (IL-2). Transduced cells were highly sensitive to minute amounts of ganciclovir (GCV) and synthesized moderate amounts of the respective cytokines. A number of cell clones were tested for the cytokine production. The two best producer cell lines, the GM-CSF-producing cells denoted B9 and the IL-2-producing cells denoted 181, were selected for further experiments. Neither B9 nor 181 cells were tumorigenic in syngeneic animals. As inducers of antitumour immunity against challenge with MK16 cells, B9 cells proved superior to the 181 cells. GCV treatment did not markedly influence the level of immunity induced.
Jinoch
Pavel
P
Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128-20 Prague 2, Czech Republic.
Zak
Roman
R
Janousková
Olga
O
Kunke
David
D
Rittich
Simon
S
Duskova
Martina
M
Sobotkova
Eva
E
Marinov
Iuri
I
Andelova
Monika
M
Smahel
Michal
M
Vonka
Vladimir
V
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006561:Herpes Simplex / Q000201:enzymology*; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D010957:Plasmids / Q000378:metabolism; D012097:Repressor Proteins; D013154:Spleen / Q000166:cytology; D013937:Thymidine Kinase / Q000235:genetics*; D013997:Time Factors
D016207:Cytokines; C068651:E6 protein, Human papillomavirus type 16; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D002857:Chromium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase; D015774:Ganciclovir