Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate.
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.
Salcedo
Margarita
M
IDM Research Laboratory, 15 rue de l'Ecole de Médecine, 75006 Paris, France. msalcedo@idm-biotech.com
Bercovici
Nadège
N
Taylor
Rachel
R
Vereecken
Pierre
P
Massicard
Séverine
S
Duriau
Dominique
D
Vernel-Pauillac
Frédérique
F
Boyer
Aurélie
A
Baron-Bodo
Véronique
V
Mallard
Eric
E
Bartholeyns
Jacques
J
Goxe
Béatrice
B
Latour
Nathalie
N
Leroy
Sophie
S
Prigent
Didier
D
Martiat
Philippe
P
Sales
François
F
Laporte
Marianne
M
Bruyns
Catherine
C
Romet-Lemonne
Jean-Loup
JL
Abastado
Jean-Pierre
JP
Lehmann
Frédéric
F
Velu
Thierry
T
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D016895:Culture Media, Serum-Free; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015789:HLA-A2 Antigen / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage; D006801:Humans; D007267:Injections; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D018793:Interleukin-13 / Q000494:pharmacology; D007519:Isoantigens / Q000008:administration & dosage / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013745:Tetanus Toxoid / Q000008:administration & dosage; D014020:Tissue Extracts / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016895:Culture Media, Serum-Free; D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens; D018793:Interleukin-13; D007519:Isoantigens; D013745:Tetanus Toxoid; D014020:Tissue Extracts; D016178:Granulocyte-Macrophage Colony-Stimulating Factor