Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to secrete interleukin 2.
Adoptive immunogene therapy of cancer is not widely studied, although it has been proposed as a promising strategy for cancer gene therapy. One of the major obstacles to this approach is the difficulty in introducing cytokine genes efficiently into T lymphocytes. In this report, we developed an adoptive immunotherapy model with murine tumor-specific cytotoxic T lymphocytes. By using an adenoviral vector, we achieved up to 100% gene transduction of murine T lymphocytes. Treatment of mice with the cytotoxic T lymphocytes genetically modified to produce interleukin 2 resulted in reduction of tumor metastasis and longer survival from intracerebral tumor death, providing a hopeful strategy for treatments of human cancers.
Nakamura
Y
Y
Department of Molecular Biotherapy Research, Japanese Foundation for Cancer Research, Tokyo.
Wakimoto
H
H
Abe
J
J
Kanegae
Y
Y
Saito
I
I
Aoyagi
M
M
Hirakawa
K
K
Hamada
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000939:Epitopes; D005260:Female; D005819:Genetic Markers; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000637:transplantation*; D008546:Melanoma, Experimental / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016176:T-Lymphocyte Subsets / Q000637:transplantation*; D014162:Transfection
D000939:Epitopes; D005819:Genetic Markers; D007376:Interleukin-2; D015851:Interleukin-7