Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate.
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-alpha+PGE2) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days. A total of 4 x 10(6) 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.
Department of Immunology, Hospital Clinic, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain. rvilella@medicina.ub.es
R
R
Vilella
D
D
Benítez
J
J
Milà
M
M
Lozano
R
R
Vilana
J
J
Pomes
X
X
Tomas
J
J
Costa
A
A
Vilalta
J
J
Malvehy
S
S
Puig
B
B
Mellado
R
R
Martí
T
T
Castel
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor