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Cancer Immunology, Immunotherapy

, Volume 56, Issue 5, pp 659–675 | Cite as

T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells

  • Jon Amund KyteEmail author
  • Gunnar Kvalheim
  • Kari Lislerud
  • Per thor Straten
  • Svein Dueland
  • Steinar Aamdal
  • Gustav Gaudernack
Original Article

Abstract

We have developed an individualized melanoma vaccine based on autologous dendritic cells (DCs) transfected with autologous tumor-mRNA. The vaccine targets the unique spectrum of tumor antigens in each patient and may recruit multiple T cell clones. In a recent phase I/II trial, we demonstrated T cell responses against vaccine antigens in 9/19 patients evaluable by T cell assays. Here, we report a follow-up study that was conducted to characterize interesting T cell responses and to investigate the effects of long-term booster vaccination. Two patients were selected for continued vaccine therapy. The clinical follow-up suggested a favorable clinical development in both patients. The immunological data (T cell proliferation/IFNγ ELISPOT/Bioplex cytokine assays) indicated sustained T cell responses and suggested an enhancing effect of booster vaccinations. Both CD4+ and CD8+ T cell responses were demonstrated. From post-vaccination samples, we generated 39 T cell clones that responded specifically to stimulation by mRNA-transfected DCs and 12 clones that responded to mock-transfected DCs. These data clearly indicate a two-component vaccine response, against transfected and non-transfected antigens. T cell receptor (TCR) clonotype mapping, performed on 11 tDC-specific clones, demonstrated that 10/11 clones had different TCRs. The results thus indicate a broad spectrum T cell response against antigens encoded by the transfected tumor-mRNA. We generally observed mixed Th1/Th2 cytokine profiles, even in T cell clones that were confirmed to be derived from a single cell. This finding suggests that cytokine patterns after cancer vaccination may be more complex than indicated by the classic Th1/Th2 dichotomy.

Keywords

Dendritic cells RNA transfection Immuno-gene therapy Melanoma T cell responses Cytokine profiles 

Abbreviations

DC

Dendritic cell

PBMC

Peripheral blood mononuclear cell

TCR

T cell receptor

DTH

Delayed-type hypersensitivity

Notes

Acknowledgment

This work was supported by the Norwegian Ministry of Health (Gene Therapy Grant), the Norwegian Cancer Society and ENACT.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Jon Amund Kyte
    • 1
    Email author
  • Gunnar Kvalheim
    • 2
  • Kari Lislerud
    • 1
  • Per thor Straten
    • 3
  • Svein Dueland
    • 4
  • Steinar Aamdal
    • 4
  • Gustav Gaudernack
    • 1
  1. 1.Section for Immunotherapy, Department of Immunology, Cancer Research InstituteThe Norwegian Radium Hospital, University of OsloOsloNorway
  2. 2.Laboratory for Cellular TherapyThe Norwegian Radium HospitalOsloNorway
  3. 3.Tumor Immunology Group, Institute of Cancer BiologyDanish Cancer SocietyCopenhagenDenmark
  4. 4.Department of Clinical Cancer ResearchThe Norwegian Radium HospitalOsloNorway

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