A Phase I/II Trial of HER2 Vaccine–Primed Autologous T-Cell Infusions in Patients with Treatment Refractory HER2–Overexpressing Breast Cancer

Purpose: High levels of type I T cells are needed for tumor eradication. We evaluated whether the HER2-specific vaccine–primed T cells are readily expanded ex vivo to achieve levels needed for therapeutic infusion. Patients and Methods: Phase I/II nonrandomized trial of escalating doses of ex vivo–expanded HER2-specific T cells after in vivo priming with a multiple peptide–based HER2 intracellular domain (ICD) vaccine. Vaccines were given weekly for a total of three immunizations. Two weeks after the third vaccine, patients underwent leukapheresis for T-cell expansion, then received three escalating cell doses over 7- to 10-day intervals. Booster vaccines were administered after the T-cell infusions. The primary objective was safety. The secondary objectives included extent and persistence of HER2-specific T cells, development of epitope spreading, and clinical response. Patients received a CT scan prior to enrollment and 1 month after the last T-cell infusion. Results: Nineteen patients received T-cell infusions. Treatment was well tolerated. One month after the last T-cell infusion, 82% of patients had significantly augmented T cells to at least one of the immunizing epitopes and 81% of patients demonstrated enhanced intramolecular epitope spreading compared with baseline (P < 0.05). There were no complete responses, one partial response (6%), and eight patients with stable disease (47%), for a disease control rate of 53%. The median survival for those with progressive disease was 20.5 months and for responders (PR+SD) was 45.0 months. Conclusions: Adoptive transfer of HER2 vaccine–primed T cells was feasible, was associated with minimal toxicity, and resulted in an increased overall survival in responding patients.