Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.
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 peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical st...
| Glavni autori: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Jezik: | English |
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2012
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| _version_ | 1826263133344235520 |
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| author | Goldinger, S Dummer, R Baumgaertner, P Mihic-Probst, D Schwarz, K Hammann-Haenni, A Willers, J Geldhof, C Prior, J Kündig, T Michielin, O Bachmann, M Speiser, D |
| author_facet | Goldinger, S Dummer, R Baumgaertner, P Mihic-Probst, D Schwarz, K Hammann-Haenni, A Willers, J Geldhof, C Prior, J Kündig, T Michielin, O Bachmann, M Speiser, D |
| author_sort | Goldinger, S |
| collection | OXFORD |
| description | 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 peptide(16-35) 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. |
| first_indexed | 2024-03-06T19:46:51Z |
| format | Journal article |
| id | oxford-uuid:2297a0af-a6c4-4ea2-9cf4-4d1e545bf4a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:46:51Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:2297a0af-a6c4-4ea2-9cf4-4d1e545bf4a72022-03-26T11:39:41ZNano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2297a0af-a6c4-4ea2-9cf4-4d1e545bf4a7EnglishSymplectic Elements at Oxford2012Goldinger, SDummer, RBaumgaertner, PMihic-Probst, DSchwarz, KHammann-Haenni, AWillers, JGeldhof, CPrior, JKündig, TMichielin, OBachmann, MSpeiser, DOptimal 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 peptide(16-35) 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. |
| spellingShingle | Goldinger, S Dummer, R Baumgaertner, P Mihic-Probst, D Schwarz, K Hammann-Haenni, A Willers, J Geldhof, C Prior, J Kündig, T Michielin, O Bachmann, M Speiser, D Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title | Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title_full | Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title_fullStr | Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title_full_unstemmed | Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title_short | Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients. |
| title_sort | nano particle vaccination combined with tlr 7 and 9 ligands triggers memory and effector cd8⁺ t cell responses in melanoma patients |
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