Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Journal 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 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.

Authors: Goldinger, S; Dummer, R; Baumgaertner, P; Mihic-Probst, D; Schwarz, K

• Publication status: Published
• Journal: European journal of immunology
• Volume: 42
• Issue: 11
• Pages: 3049-3061
• Publication date: 2012-11-01
• DOI: 10.1002/eji.201142361
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Freund's Adjuvant; Skin Neoplasms; Aminoquinolines; Statistics, Nonparametric; Adjuvants, Immunologic; Toll-Like Receptor 7; Cancer Vaccines; Nanoparticles; Lipids; Ligands; Immunologic Memory; Oligodeoxyribonucleotides; Humans; CD8-Positive T-Lymphocytes; Melanoma; Toll-Like Receptor 9; Flow Cytometry; MART-1 Antigen