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MULTIPLE ASPECTS OF NATURAL KILLER CELL EXPANSION IN RELEVANCE TO IMMUNOTHERAPY FOR HEMATOLOGIC MALIGNANCIES

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Date Issued:
2012
Abstract/Description:
Natural Killer (NK) cells are a subset of lymphocytes that regulate adaptive immune responses and utilize "missing self" recognition to activate anti-tumor and anti-viral cytotoxicity. Clinical research, as well as murine and ex vivo models, have shown that a variety of NK cell applications have proven useful as immunotherapeutic treatments for patients with hematologic malignancies. However, the selective expansion of NK cells to yield relevant amounts of these lymphocytes has been a major hurdle in the development of methods for clinical therapeutic use. Here, we demonstrate a novel ex vivo expansion method utilizing k562 leukemic cell lines and soluble cytokines as well as a novel method utilizing isolated plasma membranes of genetically engineered tumor cell lines that could be of relevance to in vivo NK cell expansion. Also, the ligand expression by canonical feeder cell lines used for NK cell expansion and our isolated plasma membranes were compared via ligand quantification by western blot quantification of 4-1BB ligand. In an adjunct study, we sought to better characterize these expansion environments by investigating the glucose metabolism of NK cells using fluorescent glucose analog 2-(N-(7-Nitrobenz-2-oxa-1, 3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) and the glycolysis inhibitor 2-Deoxy-D-Glucose (2-DG).
Title: MULTIPLE ASPECTS OF NATURAL KILLER CELL EXPANSION IN RELEVANCE TO IMMUNOTHERAPY FOR HEMATOLOGIC MALIGNANCIES.
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Name(s): Colosimo, Dominic , Author
Borgon, Robert, Committee Chair
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2012
Publisher: University of Central Florida
Language(s): English
Abstract/Description: Natural Killer (NK) cells are a subset of lymphocytes that regulate adaptive immune responses and utilize "missing self" recognition to activate anti-tumor and anti-viral cytotoxicity. Clinical research, as well as murine and ex vivo models, have shown that a variety of NK cell applications have proven useful as immunotherapeutic treatments for patients with hematologic malignancies. However, the selective expansion of NK cells to yield relevant amounts of these lymphocytes has been a major hurdle in the development of methods for clinical therapeutic use. Here, we demonstrate a novel ex vivo expansion method utilizing k562 leukemic cell lines and soluble cytokines as well as a novel method utilizing isolated plasma membranes of genetically engineered tumor cell lines that could be of relevance to in vivo NK cell expansion. Also, the ligand expression by canonical feeder cell lines used for NK cell expansion and our isolated plasma membranes were compared via ligand quantification by western blot quantification of 4-1BB ligand. In an adjunct study, we sought to better characterize these expansion environments by investigating the glucose metabolism of NK cells using fluorescent glucose analog 2-(N-(7-Nitrobenz-2-oxa-1, 3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) and the glycolysis inhibitor 2-Deoxy-D-Glucose (2-DG).
Identifier: CFH0004252 (IID), ucf:44917 (fedora)
Note(s): 2012-08-01
B.S.
Medicine, Burnett School of Biomedical Sciences
Bachelors
This record was generated from author submitted information.
Subject(s): NK
natural killer cell
hematologic malignancy
leukemia
immunotherapy
glucose uptake
expansion
transplant
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFH0004252
Restrictions on Access: public 2012-08-01
Host Institution: UCF

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