IL-12-engineered dendritic cells serve as effective tumor vaccine adjuvants in vivo.
The recent identification of tumor-associated antigens (TAA) and TAA-derived peptides presented by MHC molecules to T cells has provided the tools to design and test clinical vaccines for treating human malignancies, such as melanoma. While the most effective adjuvant for use in vaccine formulation remains unclear, autologous dendritic cells (DC) appear to be good candidate adjuvants. We have previously shown that syngeneic bone marrow-derived DC when pulsed ex vivo with relevant TAA-derived peptides can effectively vaccinate mice against a subsequent challenge with tumor or can effectively treat animals bearing established tumors. In this report, we have engineered murine interleukin-12 (mIL-12), a potent stimulator of cell-mediated immunity, into murine DC using retroviral-mediated or plasmid-based transfection procedures. Transfectants produced up to 25 ng rIL-12/10(6) cells/48 hours. These engineered cells are capable of promoting enhanced anti-tumor, antigen-specific CTL responses compared to nontransduced DC.
Zitvogel
L
L
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Couderc
B
B
Mayordomo
J I
JI
Robbins
P D
PD
Lotze
M T
MT
Storkus
W J
WJ
D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells; D005260:Female; D005354:Fibrosarcoma / Q000628:therapy; D015316:Genetic Therapy; D007111:Immunity, Cellular; D007167:Immunotherapy; D018664:Interleukin-12 / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D012513:Sarcoma, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides; D018664:Interleukin-12