A phase I trial of a multi-epitope cancer vaccine (EP-2101) in non-small cell lung (NSCLC) and colon cancer patients.

2525 Background: Effective vaccines that mediate clinical responses in cancer patients may require generation of broadly specific cytotoxic T lymphocytes (CTLs) directed against multiple epitopes and tumor-associated antigens (TAAs). The EP-2101 vaccine was designed to induce CTLs against epitopes in carcinoembryonic antigen (CEA), p53, HER-2/neu, and MAGE 2/3, four TAAs frequently over-expressed in NSCLC and colon cancer. Using a rational epitope identification process, 2 epitopes from each TAA were selected for vaccine development. All 8 epitopes displayed high HLA-A2 supertype binding affinity and immunogenicity in a primary in vitro induction assay. Six of the epitopes were analogs containing a single substitution which either enhanced MHC binding or stimulated heteroclitic T cell activation, and 2 epitopes were native sequences. The 8 epitopes together with CAP1-6D, a previously described heteroclitic CEA analog, and the PADRE helper T cell epitope were emulsified in Montanide ISA51 adjuvant and tested for safety and immunogenicity in HLA-A2+ NSCLC (stage IIb/IIIa) and colon (stage III) cancer patients with no detectable disease following standard treatment. METHODS: Patients received 6 EP-2101 treatments at 3 wk intervals, at a dose of 5 mg total peptide (0.5 mg/epitope). CTL responses in the peripheral blood of patients were measured using a validated interferon-gamma (IFN-γ) ELISPOT assay. RESULTS: Based on 7 patients who have completed treatment (4 colon, 3 lung), EP-2101 appears to be safe and well-tolerated. To date, IFN-γ-secreting CTL responses were observed in all three patients tested, with 1, 4, and 6 epitope responses being detected respectively. Vaccine responses against 1 native epitope and 5 analog epitopes in EP-2101 have ranged from 23-260 net spots/50,000 cells with <8 net spots detected in pre-vaccination samples. CONCLUSIONS: A cancer vaccine delivering 9 TAA epitopes can simultaneously induce CTL responses against multiple epitopes and TAAs in patients. This vaccine consisting of native and analog epitopes may provide effective immunotherapy in patients with diverse types of cancer expressing common TAAs. No significant financial relationships to disclose.

Duke Scholars

Author Michael Aaron Morse Medicine, Medical Oncology