Induction of Antigen-Specific CD8+ T cells in Melanoma Patients using a PrimeBoost Therapuetic Vaccine (48.18)

Abstract

Induction of tumour-specific CD8+ T cell responses in melanoma patients is the major aim of antigen-specific immunotherapy. This study evaluated a prime-boost immunotherapeutic vaccine (Hi-8™ MEL) in stage III/IV melanoma patients using vectors encoding a polyepitope string of seven CD8+ T cell epitopes from five melanoma antigens. T cell responses were evaluated in cryopreserved PBMC samples taken before and during treatment. CD8+ T cells specific for the immunodominant Melan-A epitope were detected by ex vivo tetramer assay in 24/36 (67%) of all patients and in 10/11 (91%) of patients that received the highest treatment dose. Eleven of 36 (31%) patients mounted an ex vivo IFN-γ ELISPOT response: 9/36 (25%) to Melan-A and 3/36 (8%) to other epitopes in the string (NY-ESO-1 and MAGE-3). Notably, the Melan-A-tetramer+ CD8+ T cells in one patient reached 7.25% and acquired a CD45RA−CCR7− effector/memory phenotype. This patient also exhibited an ELISPOT response and a partial clinical response (>12 months). Across the study, tetramer responders showed a median survival of 86 weeks versus 37 weeks for non-responders (p<0.001), indicating that Hi-8™ MEL immunotherapy can elicit melanoma-specific CD8+ T cell responses that are associated with tumour control and increased survival. Additional immune assays are underway to further elucidate the nature of these efficacious T cell responses.