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

• Published in: Journal of translational medicine Vol. 11; no. 1; p. 62
• Main Authors: Diaz, 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-03-2013; BioMed Central
• Subjects: Adenoviridae - genetics; Adenovirus; Adenoviruses; Aged; Analysis; Antibodies; Antigens; Arthralgia; Cancer; Cancer patients; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Carcinoembryonic antigen; Carcinoembryonic Antigen - genetics; Care and treatment; Clinical trials; Combined vaccines; Complications and side effects; DNA; DNA vaccines; Dosage and administration; Electroporation; Enzyme-Linked Immunosorbent Assay; ErbB-2 protein; Escherichia coli; Expression vectors; Female; Genes, erbB-2; Genetic research; Genetic Vectors; Health aspects; Heat; Humans; Immune response; Immune response (cell-mediated); Immunity (cell-mediated); Immunogenicity; Male; Medical research; Medicine, Experimental; Middle Aged; Neoplasms - therapy; Pharmaceutical industry; Plasmids; Safety and security measures; Side effects; Solid tumors; Studies; Toxins; Translation; Tumors; Vaccination; Vaccines; Vaccines, DNA - adverse effects; Vaccines, DNA - therapeutic use; United States
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-11-62

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.
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).
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.
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.
Study 1 - ClinicalTrials.gov, NCT00250419; Study 2 - ClinicalTrials.gov, NCT00647114.