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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.

Original publication

DOI

10.1002/eji.201142361

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2012

Volume

42

Pages

3049 - 3061

Keywords

Adjuvants, Immunologic, Aminoquinolines, CD8-Positive T-Lymphocytes, Cancer Vaccines, Flow Cytometry, Freund's Adjuvant, Humans, Imiquimod, Immunologic Memory, Ligands, Lipids, MART-1 Antigen, Melanoma, Nanoparticles, Oligodeoxyribonucleotides, Skin Neoplasms, Statistics, Nonparametric, Toll-Like Receptor 7, Toll-Like Receptor 9