Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity.
Recently, several studies have shown that vaccine therapy using dendritic cells (DCs) genetically engineered to express a surrogate tumor antigen can effectively induce antitumor immunity. In this study, murine bone marrow DCs were adenovirally transduced with murine endogenous tumor antigen gp70 expressed in CT26 cells and granulocyte macrophage colony-stimulating factor (GM-CSF), and we examined whether antigen-specific CTL responses and therapeutic immunity could be induced in mice immunized with those genetically modified DCs. The cytotoxic activity against CT26 in mice immunized with gp70-transduced DCs was significantly higher than that in control (P < 0.01) and was enhanced by GM-CSF-cotransduction (P < 0.001). GM-CSF gene transfer into DCs expressing tumor-associated antigen enhances CC chemokine receptor 7 expression on DCs, leading to improved migratory capacity of DCs to draining lymph nodes. Consequently, an effective antitumor immune response would be induced. Vaccination using gp70-transduced DCs provided remarkable therapeutic efficacy in s.c. models. Moreover, it could be sufficiently augmented by GM-CSF-cotransduction of DCs. These results support that vaccination therapy using DCs simultaneously transduced with tumor-associated antigen can elicit potent CTL response, and GM-CSF-cotransduction of DCs could optimize therapeutic response. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.
Nakamura
Masaki
M
Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama 641-8510, Japan.
Iwahashi
Makoto
M
Nakamori
Mikihito
M
Ueda
Kentaro
K
Matsuura
Ichiro
I
Noguchi
Kohei
K
Yamaue
Hiroki
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000166:cytology; D019496:Cancer Vaccines; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor