Intratumoral Administration of Secondary Lymphoid Chemokine and Unmethylated Cytosine-phosphorothioate-guanine Oligodeoxynucleotide Synergistically Inhibits Tumor Growth in Vivo.
10.3346/jkms.2011.26.10.1270
- Author:
So Mi OH
1
;
Keunhee OH
;
Dong Sup LEE
Author Information
1. Laboratory of Immunology, Transplantation Research Institute, Seoul, Korea. dlee5522@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
SLC;
CpG-ODN;
Melanoma;
Tumor Immunotherapy
- MeSH:
Animals;
Antigens, CD11c/immunology;
CD4-Positive T-Lymphocytes/immunology;
Cell Line, Tumor;
Cell Proliferation/drug effects;
Chemokine CCL21/*administration & dosage/pharmacology;
Chemotaxis, Leukocyte;
Dendritic Cells/immunology/metabolism;
Immunotherapy;
Injections, Intralesional;
Melanoma, Experimental/*immunology/*therapy;
Mice;
Mice, Inbred C57BL;
Oligodeoxyribonucleotides/*administration & dosage/pharmacology;
T-Lymphocytes/immunology/metabolism
- From:Journal of Korean Medical Science
2011;26(10):1270-1276
- CountryRepublic of Korea
- Language:English
-
Abstract:
Secondary lymphoid tissue chemokine (SLC), which is expressed in T cell zones of secondary lymphoid organs, including the spleen and lymph nodes, strongly recruits both T lymphocytes and mature dendritic cells. As appropriate interaction of tumor-specific T cells and mature dendritic cells, equipped with tumor antigens, is a prerequisite for effective T cell immunity against established tumors, we mobilized lymphocytes and dendritic cells to tumor sites by intratumoral injection of secondary lymphoid tissue chemokine-Fc (SLC-Fc) fusion protein using the B16F10 murine melanoma model. Activation of dendritic cells, another prerequisite for the effective activation of naive tumor-specific T cells, was achieved by the addition of immunostimulatory cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG-ODN) into the tumor site. Intratumoral administration of SLC-Fc or CpG-ODN revealed antitumor effects against B16F10 murine melanoma grown in the subcutaneous space. Co-treatment of SLC-Fc and CpG-ODN displayed synergistic effects in reducing the tumor size. The synergistic antitumor effect in co-treatment group was correlated with the synergistic/additive increase in the infiltration of CD4+ T cells and CD11c+ dendritic cells in the tumor mass compared to the single treatment groups. These results suggest that the combined use of chemokines and adjuvant molecules may be a possible strategy in clinical tumor immunotherapy.
