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

J Transl Med. 2013 Mar 8;11:62. doi: 10.1186/1479-5876-11-62.

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Aged
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Carcinoembryonic Antigen / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genes, erbB-2*
  • Genetic Vectors
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / therapy*
  • Plasmids
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / therapeutic use*

Substances

  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Vaccines, DNA

Associated data

  • ClinicalTrials.gov/NCT00250419
  • ClinicalTrials.gov/NCT00647114