title: Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors.
abstract: BACKGROUND
  DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease.
  
  
  METHODS
  Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2).
  
  
  RESULTS
  The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination.
  
  
  CONCLUSIONS
  V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2.
  
  
  BACKGROUND
  Study 1 - ClinicalTrials.gov, NCT00250419; Study 2 - ClinicalTrials.gov, NCT00647114.
authors.affiliation: Medical University of South Carolina, Hollings Cancer Center, Charleston, USA.
authors.forename: Claudia Marcela
authors.initials: CM
authors.lastname: Diaz
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.forename: Ansuman
authors.initials: A
authors.lastname: Bagchi
authors.forename: Jason
authors.initials: J
authors.lastname: Clark
authors.forename: Sheri
authors.initials: S
authors.lastname: Dubey
authors.forename: Arthur
authors.initials: A
authors.lastname: Fridman
authors.forename: Jesus C
authors.initials: JC
authors.lastname: Fabregas
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Elisa
authors.initials: E
authors.lastname: Scarselli
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Montero
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018734:Genes, erbB-2; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D010957:Plasmids; D019444:Vaccines, DNA / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D019444:Vaccines, DNA