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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.
European journal of immunology, November 2012, Letnik: 42, Številka: 11Journal Article
Optimal vaccine strategies must be identified for improving T‐cell vaccination against infectious and malignant diseases. MelQbG10 is a virus‐like nano‐particle loaded with A‐type CpG‐oligonucleotides (CpG‐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 MelQbG10, 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‐7R) T cells. Direct injection of MelQbG10 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 CpG‐ODN induced combined memory and effector CD8+ T‐cell responses.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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