serval:BIB_FA34B494C8D3
Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.
10.1002/eji.201142361
000369972300026
22806397
Goldinger
S.M.
author
Dummer
R.
author
Baumgaertner
P.
author
Mihic-Probst
D.
author
Schwarz
K.
author
Hammann-Haenni
A.
author
Willers
J.
author
Geldhof
C.
author
Prior
J.O.
author
Kündig
T.M.
author
Michielin
O.
author
Bachmann
M.F.
author
Speiser
D.E.
author
article
2012
European Journal of Immunology
1521-4141
0014-2980
journal
42
11
3049-3061
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.
Adjuvants, Immunologic/administration & dosage
Aminoquinolines/administration & dosage
CD8-Positive T-Lymphocytes/immunology
Cancer Vaccines/administration & dosage
Cancer Vaccines/adverse effects
Flow Cytometry
Freund's Adjuvant/administration & dosage
Humans
Immunologic Memory/immunology
Ligands
Lipids/administration & dosage
MART-1 Antigen/immunology
Melanoma/immunology
Melanoma/therapy
Nanoparticles/administration & dosage
Oligodeoxyribonucleotides/immunology
Skin Neoplasms/immunology
Statistics, Nonparametric
Toll-Like Receptor 7/immunology
Toll-Like Receptor 9/immunology
eng
60_published
true
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
University of Lausanne
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