Several
cancer vaccine efforts have been directed to simultaneously cotarget multiple
tumor antigens, with the intent to achieve broader immune responses and more effective control of
cancer growth. Genetic
cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid
DNA (
DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against
tumor-associated
antigens (TAAs) such as
carcinoembryonic antigen (CEA) and human
epidermal growth factor receptor-2 (HER2)/neu. Combinations of these modalities of immunization (heterologous prime-boost) can induce superior immune reactions as compared with single-modality
vaccines. We have generated a dual component-dual target genetic
cancer vaccine consisting of
a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of
Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two
tumor antigens gene constructs. The CEA/HER2
vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system. The immune response was measured by
enzyme-linked immunospot assay, flow cytometry, and ELISA. The CEA/HER2
vaccine was able to break immune tolerance against both
antigens. Induction of a T cell and antibody immune response was detected in immune-tolerant mice. Most importantly, the
vaccine was able to slow the growth of HER2/neu⁺ and CEA⁺
tumors. A significant T cell response was measured in NOD/scid-DR1 mice engrafted with human cord blood cells. In conclusion, the CEA/HER2 genetic
vaccine was immunogenic and able to confer significant
therapeutic effects. These data warrant the evaluation of this vaccination strategy in human clinical trials.