2003年7月
Reduction of CTLL-2 cytotoxicity by induction of apoptosis with a Fas-estrogen receptor chimera
CANCER SCIENCE
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- 巻
- 94
- 号
- 7
- 開始ページ
- 639
- 終了ページ
- 643
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1111/j.1349-7006.2003.tb01496.x
- 出版者・発行元
- JAPANESE CANCER ASSOC
Allogeneic bone marrow transplantation and donor lymphocyte infusion are powerful treatments for chemotherapy-resistant leukemia. Tumor eradication is attributed to a graft-versus-leukemia reaction by the donor-derived cytotoxic T lymphocytes (CTLs), but the same cell population may cause severe graft-versus-host disease. One strategy to suppress harmful CTL activity is to incorporate a suicide gene into the donor lymphocytes prior to infusion, and to destroy these cells when they aggressively attack nonmalignant host tissues. In this study, we investigated the feasibility of using a Fas-estrogen receptor fusion protein (MfasER) to control T cell-mediated cytotoxicity, based on our previous finding that the chimera transmits a Fas-mediated death signal through activation by estrogen binding. A murine CTL line CTLL-2 was transfected with a vector encoding MfasER, and the growth, viability and cytotoxic activity of the transfected cells (CTLL/MfasER) were analyzed. The expression of apoptosis-related proteins such as Fas ligand and perforin was also investigated. In the absence of estrogen, CTLL/MfasER showed similar growth to parental CTLL-2, and the killing activity was preserved. Addition of 10(-7) M estrogen induced a rapid apoptosis of CTLL/MfasER, and the cytotoxicity was severely impaired. A decrease of Fas ligand and perforin in the estrogen-treated CTLL/MfasER was seen in an immunoblot analysis. These functional and biochemical analyses showed that the estrogen-inducible apoptosis in MfasER-expressing CTLs rapidly terminated their target cell killing. The feasibility of using the MfasER-estrogen system to control graft-versus-host disease was demonstrated.
- リンク情報
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- DOI
- https://doi.org/10.1111/j.1349-7006.2003.tb01496.x
- CiNii Articles
- http://ci.nii.ac.jp/naid/10011689033
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/12841875
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000184243100013&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1111/j.1349-7006.2003.tb01496.x
- ISSN : 1347-9032
- CiNii Articles ID : 10011689033
- PubMed ID : 12841875
- Web of Science ID : WOS:000184243100013