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Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate

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Abstract

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

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Acknowledgements

we would like to thank GSK-Bio for the tetanus Toxoid and Berna Biotech for the HBs protein. We also thank all the patients who participated in the study. This work was funded in part by a European grant (Contract BIO4-97-2216 “Cellular Vaccines”) and by Sanofi-Aventis.

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Author notes

  1. Frédérique Vernel-Pauillac

    Present address: Institut Pasteur de Nouvelle Calédonie, 9-11 Avenue, Paul Doumer, Noumea

  2. Frédéric Lehmann

    Present address: Clinical R & D, GlaxoSmithKline Biologicals, Rixensart, Belgium

  3. Jean-Pierre Abastado

    Present address: Institut Cochin (Inserm U567/UMR 8104), Paris, France

Authors and Affiliations

  1. IDM Research Laboratory, 15 rue de l’Ecole de Médecine, 75006, Paris, France

    Margarita Salcedo, Nadège Bercovici, Rachel Taylor, Séverine Massicard, Frédérique Vernel-Pauillac, Aurélie Boyer, Véronique Baron-Bodo, Eric Mallard, Jacques Bartholeyns, Béatrice Goxe, Nathalie Latour, Sophie Leroy, Didier Prigent, Jean-Loup Romet-Lemonne & Jean-Pierre Abastado

  2. Erasme-Bordet Medical Oncology, ULB, Brussels, Belgium

    Pierre Vereecken, Dominique Duriau, Philippe Martiat, François Sales, Marianne Laporte, Catherine Bruyns, Frédéric Lehmann & Thierry Velu

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  1. Margarita Salcedo
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Correspondence to Margarita Salcedo.

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Margarita Salcedo and Nadège Bercovici both contributed equally to this work

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Salcedo, M., Bercovici, N., Taylor, R. et al. Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother 55, 819–829 (2006). https://doi.org/10.1007/s00262-005-0078-6

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