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

Authors

  • Simone M. Goldinger,

    1. Dermatology and Pathology Departments, University Hospital of Zurich, Zurich, Switzerland
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  • Reinhard Dummer,

    1. Dermatology and Pathology Departments, University Hospital of Zurich, Zurich, Switzerland
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  • Petra Baumgaertner,

    1. Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    2. Nuclear Medicine Department, University Hospital Center, Lausanne, Switzerland
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  • Daniela Mihic-Probst,

    1. Dermatology and Pathology Departments, University Hospital of Zurich, Zurich, Switzerland
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  • Katrin Schwarz,

    1. Cytos Biotechnology AG, Schlieren-Zurich, Switzerland
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  • Anya Hammann-Haenni,

    1. Cytos Biotechnology AG, Schlieren-Zurich, Switzerland
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  • Joerg Willers,

    1. Cytos Biotechnology AG, Schlieren-Zurich, Switzerland
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  • Christine Geldhof,

    1. Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    2. Nuclear Medicine Department, University Hospital Center, Lausanne, Switzerland
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  • John O. Prior,

    1. Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    2. Nuclear Medicine Department, University Hospital Center, Lausanne, Switzerland
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  • Thomas M. Kündig,

    1. Dermatology and Pathology Departments, University Hospital of Zurich, Zurich, Switzerland
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  • Olivier Michielin,

    1. Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    2. Nuclear Medicine Department, University Hospital Center, Lausanne, Switzerland
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  • Martin F. Bachmann,

    1. Cytos Biotechnology AG, Schlieren-Zurich, Switzerland
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  • Daniel E. Speiser

    Corresponding author
    1. Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    2. Nuclear Medicine Department, University Hospital Center, Lausanne, Switzerland
    • Full Correspondence: Prof. Daniel E. Speiser, Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, CHUV HO 05/1552, Av. Pierre-Decker 4, CH-1011 Lausanne, Switzerland

      Fax: +41-21-314-74-77

      e-mail: doc@dspeiser.ch

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Errata

This article is corrected by:

  1. Errata: Corrections Volume 46, Issue 2, 493, Article first published online: 3 February 2016
  2. Errata: Corrections Volume 46, Issue 2, 493, Article first published online: 3 February 2016

Abstract

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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