The crucial role of HER2 in epithelial transformation and its selective overexpression on
cancer tissues makes it an ideal target for cancer immunotherapies such as passive
immunotherapy withTrastuzumab.There are, however, a number of concerns regarding the
use of monoclonal antibodies which include resistance, repeated treatments, considerable
costs, and side effects that make active immunotherapies against HER2 desirable alternative
approaches.The efficacy of anti-HER2 DNA vaccination has been widely demonstrated
in transgenic cancer-prone mice, which recapitulate several features of human breast cancers.
Nonetheless, the rational design of a cancer vaccine able to trigger a long-lasting
immunity, and thus prevent tumor recurrence in patients, would require the understanding
of how tolerance and immunosuppression regulate antitumor immune responses and,
at the same time, the identification of the most immunogenic portions of the target protein.
We herein retrace the findings that led to our most promising DNA vaccines that, by
encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance.
Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for
their use in an ongoing Phase I clinical trial (EudraCT 2011-001104-34)
