Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction.
Although dendritic cell (DC)-based immunotherapy is considered a promising approach for cancer treatment, a large quantity of DC vaccine is required for effective sensitization/activation of immune cells because of the poor migratory ability of administered DCs into regional lymphoid tissue. In this study, we created a DC vaccine sufficiently transduced with CC chemokine receptor-7 gene (CCR7/DCs) by applying RGD fiber-mutant adenovirus vector (AdRGD), and investigated its immunological characteristics and therapeutic efficacy. CCR7/DCs acquired strong chemotactic activity for CC chemokine ligand-21 (CCL21) and exhibited an immunophenotype similar to mature DCs but not immature DCs with regard to major histocompatibility complex/costimulatory molecule-expression levels and allogenic T cell proliferation-stimulating ability, while maintaining inherent endocytotic activity. Importantly, CCR7/DCs injected intradermally into mice could accumulate in draining lymph nodes about 5.5-fold more efficiently than control AdRGD-applied DCs. Reflecting these properties of CCR7/DCs, DC vaccine genetically engineered to simultaneously express endogenous antigen and CCR7 could elicit more effective antigen-specific immune response in vivo using a lower dosage than DC vaccine transduced with antigen alone. Therefore, the application of CCR7/DCs having positive migratory ability to lymphoid tissues may contribute to reduction of efforts and costs associated with DC vaccine preparation by considerably reducing the DC vaccine dosage needed to achieve effective treatment by DC-based immunotherapy.
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan.
N
N
Okada
N
N
Mori
R
R
Koretomo
Y
Y
Okada
T
T
Nakayama
O
O
Yoshie
H
H
Mizuguchi
T
T
Hayakawa
S
S
Nakagawa
T
T
Mayumi
T
T
Fujita
A
A
Yamamoto
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002460:Cell Line; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods
D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine