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Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate

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Abstract

Eleven AJCC stage IV melanoma patients with progressive disease after treatment with biochemotherapy were treated with autologous dendritic cells pulsed with heterologous tumor cell lysates. The vaccine used mature DCs (CD1a+++, CD40++, CD80++, CD83+, and CD86+++) generated from peripheral blood monocytes in the presence of GM-CSF and IL-4. After 7 days, DCs were matured with a defined cocktail of cytokines (IL-1+IL-6+TNF-α+PGE2) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days. A total of 4×106 DCs was injected monthly under ultrasound control in an inguinal lymph node of normal appearance. The study was closed when all patients died as a consequence of tumor progression. No sign of toxicity was observed during the study. One patient experienced a partial response lasting 5 months, and two patients showed a mixed response which lasted 3 months. The median survival of the whole group was 7.3 months (range 3–14 months). This vaccination program had specific antitumoral activity in highly pretreated and large tumor burden stage IV melanoma patients and was well tolerated. The clinical responses and the median survival of the group of patients, together with the low toxicity of our DC vaccine, suggest that this approach could be applied to earlier AJCC stage IV melanoma patients.

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Acknowledgements

This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS 99/0129 and FIS 02/0364). The authors are grateful to Maria Sala and Lucia Millan for technical assistance.

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Authors and Affiliations

  1. Department of Immunology, Hospital Clinic, IDIBAPS, Villarroel 170, 08036, Barcelona, Spain

    R. Vilella, D. Benítez & J. Milà

  2. Department of Hemotherapy-Haemostasis, Hospital Clinic, IDIBAPS, Barcelona, Spain

    M. Lozano

  3. Department of Radiology, Hospital Clinic, IDIBAPS, Barcelona, Spain

    R. Vilana, J. Pomes & X. Tomas

  4. Department of Microbiology, Hospital Clinic, IDIBAPS, Barcelona, Spain

    J. Costa

  5. Department of Dermatology, Hospital Clinic, IDIBAPS, Barcelona, Spain

    A. Vilalta, J. Malvehy, S. Puig, R. Martí & T. Castel

  6. Department of Oncology, Hospital Clinic, IDIBAPS, Barcelona, Spain

    B. Mellado

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  1. R. Vilella
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Correspondence to R. Vilella.

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Vilella, R., Benítez, D., Milà, J. et al. Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate. Cancer Immunol Immunother 53, 651–658 (2004). https://doi.org/10.1007/s00262-003-0495-3

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  • DOI: https://doi.org/10.1007/s00262-003-0495-3

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