Dendritic cells modified to express fractalkine/CX3CL1 in the treatment of preexisting tumors.

Abstract

Fractalkine (CX3CL1) is a unique membrane-bound CX3C chemokine that serves as a potent chemoattractant for lymphocytes. The hypothesis of this study is that dendritic cells (DC) genetically modified ex vivo to overexpress fractalkine would enhance the T cell-mediated cellular immune response with a consequent induction of anti-tumor immunity to suppress tumor growth. To prove this hypothesis, established tumors of different mouse cancer cells (B16-F10 melanoma, H-2b, and Colon-26 colon adenocarcinoma, H-2d) were treated with intratumoral injection of bone marrow-derived DC that had been modified in vitro with an RGD fiber-mutant adenovirus vector expressing mouse fractalkine (Ad-FKN). In both tumor models tested, treatment of tumor-bearing mice with Ad-FKN-transduced DC gave rise to a significant suppression of tumor growth along with survival advantages in the treated mice. Immunohistochemical analysis of tumors treated with direct injection of Ad-FKN-transduced DC demonstrated that the treatment prompted CD8+ T cells and CD4+ T cells to accumulate in the tumor milieu, leading to activation of immune-relevant processes. Consistent with the finding, the intratumoral administration of Ad-FKN-transduced DC evoked tumor-specific cytotoxic T lymphocytes, which ensued from in vivo priming of Th1 immune responses in the treated host. In addition, the anti-tumor effect provided by intratumoral injection of Ad-FKN-transduced DC was completely abrogated in CD4+ T cell-deficient mice as well as in CD8+ T cell-deficient mice. These results support the concept that genetic modification of DC with a recombinant fractalkine adenovirus vector may be a useful strategy for cancer immunotherapy protocols.

• Authors: Mio Nukiwa, Sita Andarini, Jamal Zaini, Hong Xin, Masahiko Kanehira, Takuji Suzuki, Tatsuro Fukuhara, Hiroyuki Mizuguchi, Takao Hayakawa, Yasuo Saijo, Toshihiro Nukiwa, Toshiaki Kikuchi
• Journal: European journal of immunology (Eur J Immunol) Vol. 36 Issue 4 Pg. 1019-27 (Apr 2006) ISSN: 0014-2980 [Print] Germany
• PMID: 16525992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CX3CL1
• Chemokines, CX3C
• Cx3cl1 protein, mouse
• Membrane Proteins

Topics

• Adenoviridae
• Animals
• Cell Line, Tumor
• Chemokine CX3CL1
• Chemokines, CX3C (genetics, immunology)
• Dendritic Cells (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Genetic Therapy
• Genetic Vectors
• Immunohistochemistry
• Immunotherapy
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasms, Experimental (genetics, immunology, therapy)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)
• Transduction, Genetic