title: Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor.
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.
authors.affiliation: Department of Nuclear Medicine and.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine and.
authors.forename: Thoudam Debraj
authors.initials: TD
authors.lastname: Singh
authors.affiliation: Department of Nuclear Medicine and.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Kyungpook National University, Daegu, Korea; and.
authors.forename: Jeoung-Hee
authors.initials: JH
authors.lastname: Ha
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
authors.affiliation: Department of Nuclear Medicine and.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
authors.affiliation: Department of Nuclear Medicine and jeon9014@gmail.com jaetae@knu.ac.kr.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: Department of Nuclear Medicine and jeon9014@gmail.com jaetae@knu.ac.kr.
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3 / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology*; D005910:Glioma / Q000276:immunology / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3
keywords: Renilla luciferase; glioma; molecular imaging