In vivo antitumor effect of cytotoxic T lymphocytes engineered to produce interferon-gamma by adenovirus-mediated genetic transduction.
Immunotherapy with adoptive transfer of genetically-modified cytotoxic T lymphocytes (CTL) is a promising approach for cancer gene therapy. We developed an adoptive therapy model with murine tumor-specific CTL, to which very efficient (up to 100%) gene introduction was achieved by using recombinant adenoviral vectors. Through a comparative study on the antitumor effects of CTL genetically modified with cytokine genes, transduction with interferon-gamma gene resulted in a prominent increase in therapeutic efficacy of CTL in both metastatic and subcutaneous tumor models. Further additive effect was obtained by the adoptive cellular therapy in combination with vaccination of cytokine gene-modified tumor cells. Our findings provide a hopeful strategy of adoptive immunotherapy for human cancers.
Abe
J
J
Department of Molecular Biotherapy Research, Cancer Institute, Tokyo, Japan.
Wakimoto
H
H
Tsunoda
R
R
Okabe
S
S
Yoshida
Y
Y
Aoyagi
M
M
Hirakawa
K
K
Hamada
H
H
D000256:Adenoviridae; D000818:Animals; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma