Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma.
We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.
Soiffer
R
R
Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Lynch
T
T
Mihm
M
M
Jung
K
K
Rhuda
C
C
Schmollinger
J C
JC
Hodi
F S
FS
Liebster
L
L
Lam
P
P
Mentzer
S
S
Singer
S
S
Tanabe
K K
KK
Cosimi
A B
AB
Duda
R
R
Sober
A
A
Bhan
A
A
Daley
J
J
Neuberg
D
D
Parry
G
G
Rokovich
J
J
Richards
L
L
Drayer
J
J
Berns
A
A
Clift
S
S
Cohen
L K
LK
Mulligan
R C
RC
Dranoff
G
G
D019496:Cancer Vaccines / Q000009:adverse effects; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005818:Genetic Engineering; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D006968:Hypersensitivity, Delayed; D008214:Lymphocytes / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014182:Transplantation, Autologous
D019496:Cancer Vaccines; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor