NIH Research Festival
We have developed a therapeutic cancer vaccine targeting HER2, a driver oncogene often associated with worse outcome, using autologous dendritic cells (DCs) transduced with an adenoviral vector (AdHER2). In mice, the homologous vaccine cured virtually all mice with established tumors and macroscopic lung metastases. The protection was dependent on antibodies against HER2 that inhibited HER2 phosphorylation, but was FcR (ADCC)-independent, unlike the mechanism of trastuzumab. This is a phase I clinical trial in patients with metastatic cancers who have progressed after a minimum of one standard therapy, whose tumor is HER2 immunohistochemistry (IHC) score ≥1+ or HER2/CEP17 ratio ≥ 1.8 by FISH. In Part 1 enrolling enrolled patients naïve to HER2-directed therapies, at the second and third dose level (10 and 20x10^6, n=6 each), 45% (N=5/11) had clinical benefit; one CR (89 weeks, ovarian carcinoma), one PR (24 weeks, gastric adenocarcinoma, and 3 SDs (1 ovarian carcinosarcoma and 2 colon cancers). The patient with a CR (HER2 IHC score 3+, FISH HER2/CEP17 ratio 1.3) recurred with HER2 IHC score 0, and the patient with ovarian carcinosarcoma (HER2 IHC score 1+ and FISH HER2/CEP17 ratio 1.0) with initial response (-24.8%) progressed with new lesions (HER2 IHC score 0), suggesting immune escape. Adverse reactions were G1 injection-site reactions. We have translated a cancer vaccine from mice to humans with promising early results. We intend to combine this vaccine with checkpoint inhibitors, as vaccines can turn “cold” tumors into “hot” ones to overcome limited response rate and efficacy.
Scientific Focus Area: Cancer Biology
This page was last updated on Friday, March 26, 2021