Intratumoral administration of secondary lymphoid chemokine and unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotide synergistically inhibits tumor growth in vivo.

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 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.

• Authors: So Mi Oh, Keunhee Oh, Dong-Sup Lee
• Journal: Journal of Korean medical science (J Korean Med Sci) Vol. 26 Issue 10 Pg. 1270-6 (Oct 2011) ISSN: 1598-6357 [Electronic] Korea (South)
• PMID: 22022177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD11c Antigen
• CPG-oligonucleotide
• Chemokine CCL21
• Oligodeoxyribonucleotides

Topics

• Animals
• CD11c Antigen (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)