title: Intratumoral delivery of recombinant vaccinia virus encoding for ErbB2/Neu inhibits the growth of salivary gland carcinoma cells.
abstract: BACKGROUND
  The antitumor activity induced by intratumoral vaccination with poxvirus expressing a tumor antigen was shown to be superior to that induced by subcutaneous vaccination. Salivary gland carcinomas overexpress ErbB2. Trastuzumab, a monoclonal antibody to ErbB2, was proposed for salivary gland tumors treatment. We explored the effectiveness of intratumoral vaccination with the recombinant vaccinia virus ErbB2/Neu (rV-neuT) vaccine in hampering the growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells (SALTO) in BALB-neuT mice.
  
  
  METHODS
  BALB-neuT male mice were subcutaneously injected with SALTO tumor cells and intratumorally vaccinated twice with different doses of either rV-neuT or V-wt (wild-type). Tumors were measured weekly. The presence of anti-ErbB2/Neu antibodies was assayed by ELISA, immunoprecipitation or indirect immunofluorescence. Biological activity of immune sera was investigated by analyzing antibody-dependent cellular cytotoxicity (ADCC), SALTO cells proliferation and apoptosis, ErbB2/Neu receptor down regulation and ERK1/2 phosphorylation. Anti-Neu T cell immunity was investigated by determining the release of IL-2 and IFN-gamma in T cells supernatant. Survival curves were determined using the Kaplan-Meier method and compared using the log-rank test. Differences in tumor volumes, number of apoptotic cells, titer of the serum, percentage of ADCC were evaluated through a two-tailed Student's t-test.
  
  
  RESULTS
  rV-neuT intratumoral vaccination was able to inhibit the growth of SALTO cancer cells in a dose-dependent manner. The anti-Neu serum titer paralleled in vivo antitumor activity of rV-neuT vaccinated mice. rV-neuT immune serum was able to mediate ADCC, inhibition of SALTO cells proliferation, down regulation of the ErbB2/Neu receptor, inhibition of ERK1/2 phosphorylation and induction of apoptosis, thus suggesting potential mechanisms of in vivo tumor growth interference. In addition, spleen T cells of rV-neuT vaccinated mice released IFN-gamma and IL-2 upon in vitro stimulation with several Neu-specific peptides located in the extracellular domain of Neu sequence.
  
  
  CONCLUSIONS
  rV-neuT intratumoral vaccination could be employed to induce an efficient antitumor response and reject transplanted salivary gland tumors. Our findings may have important implications for the design of cancer vaccine protocols for the treatment of salivary gland tumors and other accessible tumors using intratumoral injection of recombinant vaccinia virus.
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Fantini
authors.forename: Monica
authors.initials: M
authors.lastname: Benvenuto
authors.forename: Pamela
authors.initials: P
authors.lastname: Sacchetti
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Giganti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tresoldi
authors.forename: Paolo
authors.initials: P
authors.lastname: Lido
authors.forename: Florigio
authors.initials: F
authors.lastname: Lista
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nanni
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Rome, Italy. bei@med.uniroma2.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018734:Genes, erbB-2; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D012468:Salivary Gland Neoplasms / Q000276:immunology / Q000473:pathology*; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines