Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate |
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Authors: | Margarita Salcedo Nadège Bercovici Rachel Taylor Pierre Vereecken Séverine Massicard Dominique Duriau Frédérique Vernel-Pauillac Aurélie Boyer Véronique Baron-Bodo Eric Mallard Jacques Bartholeyns Béatrice Goxe Nathalie Latour Sophie Leroy Didier Prigent Philippe Martiat François Sales Marianne Laporte Catherine Bruyns Jean-Loup Romet-Lemonne Jean-Pierre Abastado Frédéric Lehmann Thierry Velu |
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Institution: | (1) IDM Research Laboratory, 15 rue de l’Ecole de Médecine, 75006 Paris, France;(2) Erasme-Bordet Medical Oncology, ULB, Brussels, Belgium;(3) Present address: Institut Pasteur de Nouvelle Calédonie, 9-11 Avenue, Paul Doumer, Noumea;(4) Present address: Clinical R & D, GlaxoSmithKline Biologicals, Rixensart, Belgium;(5) Present address: Institut Cochin (Inserm U567/UMR 8104), Paris, France |
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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.
Margarita Salcedo and Nadège Bercovici both contributed equally to this work |
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Keywords: | Allogeneic melanoma lysate Dendritic cells Immunotherapy T-cell responses Human clinical trial |
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