Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine
BACKGROUND: Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epit...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2010
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| In: |
Cancer immunology immunotherapy
Year: 2010, Volume: 59, Issue: 6, Pages: 863-873 |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-009-0811-7 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00262-009-0811-7
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| Author Notes: | Adam Dangoor, Paul Lorigan, Ulrich Keilholz, Dirk Schadendorf, Adrian Harris, Christian Ottensmeier, John Smyth, Klaus Hoffmann, Richard Anderson, Martin Cripps, Joerg Schneider, Robert Hawkins |
| Summary: | BACKGROUND: Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes from five melanoma antigens. - METHODS: Forty-one HLA-A2 positive patients with stage III/IV melanoma were enrolled. Patient groups received one or two doses of DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell responses were evaluated using ex-vivo tetramer and IFN-gamma ELISPOT assays. Safety and clinical responses were monitored. - RESULTS: Prime-boost DNA/MVA induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31 (32%) patients. T cell responder rates were <50% with low-dose DNA/MVA, or MVA alone, rising to 91% with high-dose DNA/MVA. Among eight patients showing evidence of clinical benefit-one PR (24 months+), five SD (5 months+) and two mixed responses-seven had associated immune responses. Melan-A-tetramer+ immunity was associated with a median 8-week increase in time-to-progression (P = 0.037) and 71 week increase in survival (P = 0.0002) compared to non-immunity. High-dose vaccine was well tolerated. The only significant toxicities were flu-like symptoms and injection-site reactions. - CONCLUSIONS: DNA.Mel3 and MVA.Mel3 in a prime-boost protocol generated high rates of immune response to melanoma antigen epitopes. The treatment was well tolerated and the correlation of immune responses with patient outcomes encourages further investigation. |
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| Item Description: | Online veröffentlicht 31 December 2009 Gesehen am 03.08.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-009-0811-7 |