Abstract |
IL-2 is a cytokine that is essential for the expansion and survival of activated T cells. Although adoptive transfer of tumor-specific T cells with IL-2 is one of strategies for cancer immunotherapy, it is essential to replace IL-2 that exerts severe side effects in vivo. To solve this problem, we propose to use an antibody/IL-2R chimera, which can transduce a growth signal in response to a cognate antigen. We constructed two chimeras, in which ScFv of anti- fluorescein antibody was tethered to extracellular D2 domain of erythropoietin receptor and transmembrane/cytoplasmic domains of IL-2Rbeta or gamma chain. When the chimeras were co-expressed in IL-3-dependent pro-B cell line Ba/F3 and IL-2-dependent T cell line CTLL-2, gene-modified cells were selectively expanded in the absence of IL-3 and IL-2, respectively, by adding fluorescein-conjugated BSA (BSA-FL) as a cognate antigen. Growth assay revealed that the cells with the chimeras transduced a growth signal in a BSA-FL dose-dependent manner. Furthermore, STAT3, STAT5, ERK1/2 and Akt, which are hallmarks for IL-2R signaling, were all activated by the chimeras in CTLL-2 transfectant. We also demonstrated that the chimeras were functional in murine primary T cells. These results demonstrate that the antibody/IL-2R chimeras could substantially mimic the wild-type IL-2R and could specifically expand gene-modified T cells in the presence of the cognate antigen.
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Authors | Takahiro Sogo, Masahiro Kawahara, Hiroshi Ueda, Makoto Otsu, Masafumi Onodera, Hiromitsu Nakauchi, Teruyuki Nagamune |
Journal | Cytokine
(Cytokine)
Vol. 46
Issue 1
Pg. 127-36
(Apr 2009)
ISSN: 1096-0023 [Electronic] England |
PMID | 19223197
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Haptens
- Interleukin-3
- Ligands
- Receptors, Interleukin-2
- Recombinant Fusion Proteins
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Topics |
- Animals
- Cell Line
- Dimerization
- Flow Cytometry
- Haptens
(chemistry)
- Interleukin-3
(metabolism)
- Ligands
- Mice
- Models, Biological
- Protein Structure, Tertiary
- Receptors, Interleukin-2
(chemistry)
- Recombinant Fusion Proteins
(chemistry)
- Retroviridae
(metabolism)
- Signal Transduction
- T-Lymphocytes
(metabolism)
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