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Beneficial therapeutic effects with different particulate structures of murine polyomavirus VP1-coat protein carrying self or non-self CD8 T cell epitopes against murine melanoma

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Polyomavirus-like-particles (PLPs) are empty, non-replicative, non-infectious particles that represent a potent antigen-delivery system against malignant disease. Protective anti-tumour immunity can be induced under therapy conditions by subcutaneous (s.c.) treatment with particulate antigenic structures like chimerical polyomavirus-pentamers (PPs). These PPs displaying an immunodominant H-2Kb-restricted ovalbumin (OVA)257-264 epitope evoked nearly complete tumour remission in MO5 (B16-OVA) melanoma-bearing C57BL/6 mice by two s.c. applications in a weekly interval. The immunotherapeutic intervention started at day 4 after melanoma implant. Furthermore, 40% of melanoma-bearing mice vaccinated with heterologous PPs carrying a H-2Kb-restricted cytotoxic T lymphocyte (CTL) epitope derived from of tyrosinase-related protein 2 (TRP2) survived similar treatment conditions. However, a late immunotherapeutic onset at day 10 post melanoma inoculation revealed no significant differences between the therapeutic values (40–60% survival) of VP1-OVA252-270 and VP1-TRP2180-192 PPs, respectively. These experiments underlined the capacity of PPs to break T cell tolerance against a differentially expressed self-antigen. As a correlate for preventive and therapeutic immunity against MO5 melanoma the number of OVA257-264- or TRP2180-188-specific CD8 T cells were significantly increased within the splenocyte population of treated mice as measured by H-2Kb-OVA257-264-PE tetramer staining or appropriate ELISPOT assays, respectively. These results reveal that heterologous PLPs and even chimerical PPs represent highly efficient antigen carriers for inducing CTL responses underlining their potential as immunotherapeutics against cancer.

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Abbreviations

APCs:

Antigen presenting cells

CMI:

Cell-mediated immunity

CTL:

Cytotoxic T lymphocytes

DCs:

Dendritic cells

LPS:

Lipopolysaccharide

MHC:

Major histocompatibility complex

OVA:

Ovalbumin

PCS:

Photon correlation spectroscopy

PE:

Phycoerythrin

PLPs:

Murine polyomavirus-like-particles

PPs:

Murine polyomavirus-like-pentamers

TRP2:

Tyrosinase-related protein 2

VP1:

Viral protein 1 of murine polyomavirus

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Acknowledgements

This work was financially supported by the BMBF projects ‘Biochance‘ 0313044 and ‘Supramolecular Drug-Delivery-Systems’ 03C0308 A-C. Prof. K. L. Rock generously provided the MO5 melanoma cell line.

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Authors and Affiliations

  1. responsif GmbH, Schallershofer Strasse 84, 91056, Erlangen, Germany

    Marc Brinkman, Juergen Walter, Swen Grein, Michael J. W. Thies, Torsten W. Schulz, Martin Herrmann, Christian O. A. Reiser & Juergen Hess

  2. Institute for Clinical Immunology and Rheumatology, Medical Department III, University Erlangen-Nuremberg, 91054, Erlangen, Germany

    Martin Herrmann

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  1. Marc Brinkman
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  2. Juergen Walter
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  3. Swen Grein
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  4. Michael J. W. Thies
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  5. Torsten W. Schulz
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  6. Martin Herrmann
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  7. Christian O. A. Reiser
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  8. Juergen Hess
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Correspondence to Juergen Hess.

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Brinkman, M., Walter, J., Grein, S. et al. Beneficial therapeutic effects with different particulate structures of murine polyomavirus VP1-coat protein carrying self or non-self CD8 T cell epitopes against murine melanoma. Cancer Immunol Immunother 54, 611–622 (2005). https://doi.org/10.1007/s00262-004-0655-0

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  • DOI: https://doi.org/10.1007/s00262-004-0655-0

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