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- Title
Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8<sup>+</sup> T-cell responses in melanoma patients.
- Authors
Goldinger, Simone M.; Dummer, Reinhard; Baumgaertner, Petra; Mihic-Probst, Daniela; Schwarz, Katrin; Hammann-Haenni, Anya; Willers, Joerg; Geldhof, Christine; Prior, John O.; Kündig, Thomas M.; Michielin, Olivier; Bachmann, Martin F.; Speiser, Daniel E.
- Abstract
Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. Mel Qb G10 is a virus-like nano-particle loaded with A-type Cp G-oligonucleotides ( Cp G- ODN) and coupled to peptide16-35 derived from Melan- A/ MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with Mel Qb G10, given (i) with IFA ( Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan- A/ MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127+ ( IL-7 R) T cells. Direct injection of Mel Qb G10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/ CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and Cp G- ODN induced combined memory and effector CD8+ T-cell responses.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 11, p3049
- ISSN
0014-2980
- Publication type
Academic Journal
- DOI
10.1002/eji.201142361