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

作者：Diaz Montero Claudia Marcela; Chiappori Alberto; Aurisicchio Luigi; Bagchi Ansuman; Clark Jason; Dubey Sheri; Fridman Arthur; Fabregas Jesus C; Marshall John; Scarselli Elisa; La Monica Nicola; Ciliberto Gennaro; Montero Alberto J^*

来源：Journal of Translational Medicine, 2013, 11(1): 62.

DOI：10.1186/1479-5876-11-62

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

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. %26lt;br%26gt;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). %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2013-3-8