Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors

Claudia Marcela Diaz-Montero, Alberto Chiappori, Luigi Aurisicchio, Ansuman Bagchi, Jason Clark, Sheri Dubey, Arthur Fridman, Jesus C. Fabregas, John Marshall, Elisa Scarselli, Nicola La Monica, Gennaro Ciliberto, Alberto J. Montero

Research output: Contribution to journalArticlepeer-review

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. Conclusion: 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.Trial registration: Study 1 - ClinicalTrials.gov, NCT00250419; Study 2 - ClinicalTrials.gov,NCT00647114.

Original languageEnglish
Article number62
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Mar 8 2013

Keywords

  • Adenoviral vaccine
  • Cell-mediated immune response
  • DNA vaccine
  • Electroporation
  • Prime-boost
  • Solid tumors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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