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Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Cancer Gene Therapy volume 13, pages 905–918 (2006)Cite this article

Abstract

We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-γ ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.

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Acknowledgements

This work was supported by the Norwegian Ministry of Health (Gene Therapy Grant) and the Norwegian Cancer Society. We thank Mrs Anne Brunsvig, Ms Inger-Lise Haakensen, Mr Sigurd Borgen and Ms Turid Kirsti Hønnåshagen for excellent work on DC generation, and the research nurses Kristin Øwre and Lone Hegg for excellent patient care. We also thank Dr Carrie Grimsrud for helpful work on total RNA extraction and Professor Olav Kaalhus for valuable advice on statistical analysis.

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Author notes

  1. J A Kyte: Financially supported by The Norwegian Cancer Society.

  2. L Mu: Financially supported by The Norwegian Ministry of Health (Gene Therapy Grant).

Authors and Affiliations

  1. Department of Immunology, Section for Immunotherapy, Cancer Research Institute, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    J A Kyte, L Mu, K Lislerud & G Gaudernack

  2. Laboratory for Cellular Therapy, The Norwegian Radium Hospital, Oslo, Norway

    L Mu, G Kvalheim & H Hammerstad

  3. Department of Clinical Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    S Aamdal & S Dueland

  4. Department of Radiology, The Norwegian Radium Hospital, Oslo, Norway

    M Hauser

  5. Department of Plastic Surgery, The Norwegian Radium Hospital, Oslo, Norway

    H P Gullestad & T Ryder

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  1. J A Kyte
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Correspondence to J A Kyte.

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Kyte, J., Mu, L., Aamdal, S. et al. Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther 13, 905–918 (2006). https://doi.org/10.1038/sj.cgt.7700961

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