title: Experimental therapy of HPV16 induced tumors with IL12 expressed by recombinant vaccinia virus in mice.
abstract: Recombinant vaccinia viruses derived from strain Praha, clone P13, and strain MVA were used for intratumoral delivery and expression of IL12 genes in tumors induced by HPV16 E6+E7 oncogenes in mice. Intratumoral injection of 10(3) PFU of P13-IL12 virus resulted in an increase of intra-tumoral IL12 on days 6-13, while only low levels of IL12 were found in sera. After the inoculation of 10(6) PFU of MVA-IL12, the same levels of IL12 were found as in animals injected with control virus. The intratumoral inoculation of 10(3) PFU P13-IL12 resulted in only approximately 30% of the tumors being virus positive, which was a consequence of reduced multiplication of the recombinant virus in vivo. The number of virus-positive tumors was not increased by repeated inoculations on three consecutive days. Intratumoral therapy with a dose of 10(3) PFU of P13-IL12 slowed down the growth of TC1 tumors, but never caused their regression. When local P13-IL12 treatment was combined with antigen-specific, DNA-vaccination therapy, no synergy between the two treatments was observed. The treatment with IL12-expressing virus retarded tumor growth to some degree, but did not change the number of regressing tumors. The highest efficacy of intra-tumoral P13-IL12 therapy was observed when the TC-1/A9 cell subline, with downregulated MHC class I expression, was used. TC-1/A9 tumors are less refractory to treatment with 10(3) P13-IL12/EL than are parental TC-1 cells.
authors.affiliation: Institute of Hematology and Blood Transfusion, Department of Experimental Virology, 128 20 Prague 2, Czech Republic. sarkan@uhkt.cz
authors.forename: Sárka
authors.initials: S
authors.lastname: Nemeckova
authors.forename: Vojtech
authors.initials: V
authors.lastname: Sroller
authors.forename: Petr
authors.initials: P
authors.lastname: Hainz
authors.forename: Jitka
authors.initials: J
authors.lastname: Krystofova
authors.forename: Michal
authors.initials: M
authors.lastname: Smahel
authors.forename: Lud'a
authors.initials: L
authors.lastname: Kutinova
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D000882:Haplorhini; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy; D013997:Time Factors; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12