Efficient expansion of antigen specific CD8 T cells in melanoma patients immunized with peptide, IFA and CpG oligonucleotide 7909

Abstract

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It is a considerable challenge to develop therapeutic vaccines that activate T cells efficiently. Major goals are the induction of strong specific T cell expansion and effector functions in vivo, which may well result in enhanced immune protection. In this study, we tested whether a CpG oligonucleotide, 7909, by virtue of its ability to trigger dendritic cell maturation, would lead to strong activation of antigen specific CD8 T cells upon co-injection with a peptide vaccine. Eight melanoma patients received CpG 7909, mixed with Melan-A analog peptide (ELAGIGILTV) and Incomplete Freunds Adjuvant (IFA). Toxicity was mild to moderate, including well tolerated local inflammation at injection sites. Melan-A peptide specific CD8+ T cells in PBL were analyzed ex vivo with fluorescent HLA-A2/Melan-A multimers and IFNγ Elispot assays. Preliminary results demonstrate strong T cell expansion easily detectable in PBMC from 4/4 patients analyzed so far. After four vaccines, expansion of antigen specific (multimer+) T cells was up to 76 fold (mean: 31 fold). These T cell responses were significantly stronger than in patients who had received peptide + IFA without CpGs. Ongoing studies focus on T cell differentiation, effector molecule expression, and clinical responses. The results demonstrate for the first time that CpG 7909 is an efficient ’adjuvant’ enhancing peptide vaccine induced activation of human antigen specific T cells.