Gene therapy with CX3CL1/Fractalkine induces antitumor immunity to regress effectively mouse hepatocellular carcinoma.
CX3CL1/Fractalkine(FK), a chemokine existing in both secreted and membrane anchored form, was reported to induce suppressive activities in tumor models. Here, we demonstrate for the first time the antitumor effects of FK in murine hepatocellular carcinoma (HCC) by constructing a FK eukaryotic expression vector (pIRES-FK) and transferring it into such tumor cells. Tumor rejection experiments were performed by injecting FK gene-modified murine HCC cell line (MM45T.Li) into immunocompetent mice, which significantly inhibited tumorigenicity or growth of MM45T.Li-FK cells. Immunohistochemistry examination and fluorescence-activated cell sorting analyses revealed both CD4+ and CD8+ T cells infiltration within the tumor together with a marked increase of these cells in the peripheral blood. Splenic lymphocyte from mice treated with MM45T.Li-FK were effective in the induction of tumor-specific cytotoxic T cells. We also observed an increased production of IL-2 and IFN-gamma in MM45T.Li-FK tumor tissue. Our results suggest that transfer of the FK gene into tumor cells could elicit a specific antitumor immunity capable of inhibiting tumor growth which lead to increased survival of tumor-bearing hosts. FK should be considered as a chemokine suitable for cancer immunoprevention or gene therapy.
Tang
L
L
Institute of Viral Hepatitis, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Hu
H-d
HD
Hu
P
P
Lan
Y-h
YH
Peng
M-l
ML
Chen
M
M
Ren
H
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D054428:Chemokine CX3CL1 / Q000235:genetics*; D002634:Chemotaxis, Leukocyte; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000379:methods
D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma