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Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor.
Lee, Ho Won; Singh, Thoudam Debraj; Lee, Sang-Woo; Ha, Jeoung-Hee; Rehemtulla, Alnawaz; Ahn, Byeong-Cheol; Jeon, Young Hyun; Lee, Jaetae.
Afiliação
  • Lee HW; Department of Nuclear Medicine and.
  • Singh TD; Department of Nuclear Medicine and.
  • Lee SW; Department of Nuclear Medicine and.
  • Ha JH; Department of Pharmacology, Kyungpook National University, Daegu, Korea; and.
  • Rehemtulla A; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
  • Ahn BC; Department of Nuclear Medicine and.
  • Jeon YH; Department of Nuclear Medicine and jeon9014@gmail.com jaetae@knu.ac.kr.
  • Lee J; Department of Nuclear Medicine and jeon9014@gmail.com jaetae@knu.ac.kr.
FASEB J ; 28(7): 2932-41, 2014 Jul.
Article em En | MEDLINE | ID: mdl-24736413
ABSTRACT
Natural killer (NK) cell-based immunotherapy is a promising strategy for cancer treatment, and caspase-3 is an important effector molecule in NK cell-mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cell-based immunotherapy by serial noninvasive imaging of apoptosis using a caspase-3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspase-3 sensor as a surrogate marker for caspase-3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54-CR cells. Human NK92 cells were used as effector cells. Treatment with NK92 cells resulted in a time- and effector number-dependent increase in bioluminescence imaging (BLI) activity of the caspase-3 sensor in D54-CR cells in vitro. Caspase-3 activation by NK92 treatment was blocked by Z-VAD treatment in D54-CR cells. Transfusion of NK92 cells induced an increase of the BLI signal by caspase-3 activation in a dose- and time-dependent manner in D54-CR tumor-bearing mice but not in PBS-treated mice. Accordingly, sequential BLI with the Rluc reporter gene revealed marked retardation of tumor growth in the NK92-treatment group but not in the PBS-treatment group. These data suggest that noninvasive imaging of apoptosis with a caspase-3 sensor can be used as an effective tool for evaluation of therapeutic efficacy as well as for optimization of NK cell-based immunotherapy.-Lee, H. W., Singh, T. D., Lee, S.-W., Ha, J.-H., Rehemtulla, A., Ahn, B.-C., Jeon, Y.-H., Lee, J. Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Sobrevivência Celular / Apoptose / Caspase 3 / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Sobrevivência Celular / Apoptose / Caspase 3 / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article