Intratumoral administration of secondary lymphoid chemokine and unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotide synergistically inhibits tumor growth in vivo.
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 naïve 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.
Laboratory of Immunology, Transplantation Research Institute, Seoul, Korea.
So Mi
SM
Oh
Keunhee
K
Oh
Dong-Sup
DS
Lee
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054421:Chemokine CCL21 / Q000008:administration & dosage* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy; D015552:Injections, Intralesional; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D039521:CD11c Antigen; C408982:CPG-oligonucleotide; D054421:Chemokine CCL21; D009838:Oligodeoxyribonucleotides