A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients.
Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.
Trakatelli
Myrto
M
Department of Medical Oncology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.
Toungouz
Michel
M
Blocklet
Didier
D
Dodoo
Ygierne
Y
Gordower
Laurence
L
Laporte
Marianne
M
Vereecken
Pierre
P
Sales
Francois
F
Mortier
Laurent
L
Mazouz
Naima
N
Lambermont
Micheline
M
Goldman
Serge
S
Coulie
Pierre
P
Goldman
Michel
M
Velu
Thierry
T
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes; D019496:Cancer Vaccines / Q000276:immunology*; D018929:Cell Culture Techniques; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016899:Interferon-beta / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007377:Interleukin-3; D016899:Interferon-beta