Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy
Recent clinical studies suggest that adoptive transfer of donor-derived natural killer (NK) cells may improve clinical outcome in hematological malignancies and some solid tumors by direct antitumor effects as well as by reduction of graft versus host disease (GVHD). NK cells have also been shown to...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-05-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00101/full |
| _version_ | 1818418571327307776 |
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| author | Xiaokui eZhang Lin eKang Vanessa eVoskinarian-Berse Eric eLaw Tiffany eReddin Mohit eBhatia Alexandra eHariri Yuhong eNing David eDong Timothy eMaguire Martin eYarmush Wolfgang eHofgartner Stewart eAbbot Robert eHariri |
| author_facet | Xiaokui eZhang Lin eKang Vanessa eVoskinarian-Berse Eric eLaw Tiffany eReddin Mohit eBhatia Alexandra eHariri Yuhong eNing David eDong Timothy eMaguire Martin eYarmush Wolfgang eHofgartner Stewart eAbbot Robert eHariri |
| author_sort | Xiaokui eZhang |
| collection | DOAJ |
| description | Recent clinical studies suggest that adoptive transfer of donor-derived natural killer (NK) cells may improve clinical outcome in hematological malignancies and some solid tumors by direct antitumor effects as well as by reduction of graft versus host disease (GVHD). NK cells have also been shown to enhance transplant engraftment during allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. The limited ex vivo expansion potential of NK cells from peripheral blood (PB) or umbilical cord blood (UCB) has however restricted their therapeutic potential. Here we define methods to efficiently generate NK cells from donor matched, full-term human placenta perfusate (termed Human Placenta-Derived Stem Cell, HPDSC) and UCB. Following isolation from cryopreserved donor-matched HPDSC and UCB units, CD56+CD3- placenta-derived NK cells, termed pNK cells, were expanded in culture for up to 3 weeks to yield an average of 1.2 billion cells per donor that were >80% CD56+CD3-, comparable to doses previously utilized in clinical applications. Ex vivo-expanded pNK cells exhibited a marked increase in anti-tumor cytolytic activity coinciding with the significantly increased expression of NKG2D, NKp46 and NKp44 (p < 0.001, p < 0.001, and p < 0.05, respectively). Strong cytolytic activity was observed against a wide range of tumor cell lines in vitro. pNK cells display a distinct microRNA (miRNA) expression profile, immunophenotype and greater antitumor capacity in vitro compared to PB NK cells used in recent clinical trials. With further development, pNK may represent a novel and effective cellular immunotherapy for patients with high clinical needs and few other therapeutic options. |
| first_indexed | 2024-12-14T12:24:47Z |
| format | Article |
| id | doaj.art-b44c52f549e049a3a2483a3099d70304 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:24:47Z |
| publishDate | 2013-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b44c52f549e049a3a2483a3099d703042022-12-21T23:01:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-05-01410.3389/fimmu.2013.0010147209Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer ImmunotherapyXiaokui eZhang0Lin eKang1Vanessa eVoskinarian-Berse2Eric eLaw3Tiffany eReddin4Mohit eBhatia5Alexandra eHariri6Yuhong eNing7David eDong8Timothy eMaguire9Martin eYarmush10Wolfgang eHofgartner11Stewart eAbbot12Robert eHariri13Celgene Cellular TherapeuticsCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsPrinceton UniversityCelgene Signal ResearchDepartment of Biomedical Engineering, Rutgers UniversityDepartment of Biomedical Engineering, Rutgers UniversityDepartment of Biomedical Engineering, Rutgers UniversityCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsCelgene Cellular TherapeuticsRecent clinical studies suggest that adoptive transfer of donor-derived natural killer (NK) cells may improve clinical outcome in hematological malignancies and some solid tumors by direct antitumor effects as well as by reduction of graft versus host disease (GVHD). NK cells have also been shown to enhance transplant engraftment during allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. The limited ex vivo expansion potential of NK cells from peripheral blood (PB) or umbilical cord blood (UCB) has however restricted their therapeutic potential. Here we define methods to efficiently generate NK cells from donor matched, full-term human placenta perfusate (termed Human Placenta-Derived Stem Cell, HPDSC) and UCB. Following isolation from cryopreserved donor-matched HPDSC and UCB units, CD56+CD3- placenta-derived NK cells, termed pNK cells, were expanded in culture for up to 3 weeks to yield an average of 1.2 billion cells per donor that were >80% CD56+CD3-, comparable to doses previously utilized in clinical applications. Ex vivo-expanded pNK cells exhibited a marked increase in anti-tumor cytolytic activity coinciding with the significantly increased expression of NKG2D, NKp46 and NKp44 (p < 0.001, p < 0.001, and p < 0.05, respectively). Strong cytolytic activity was observed against a wide range of tumor cell lines in vitro. pNK cells display a distinct microRNA (miRNA) expression profile, immunophenotype and greater antitumor capacity in vitro compared to PB NK cells used in recent clinical trials. With further development, pNK may represent a novel and effective cellular immunotherapy for patients with high clinical needs and few other therapeutic options.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00101/fullmiRNAplacental-derived natural killer cellsex vivo expansionanti-tumor cytolytic activitycellular immunotherapy |
| spellingShingle | Xiaokui eZhang Lin eKang Vanessa eVoskinarian-Berse Eric eLaw Tiffany eReddin Mohit eBhatia Alexandra eHariri Yuhong eNing David eDong Timothy eMaguire Martin eYarmush Wolfgang eHofgartner Stewart eAbbot Robert eHariri Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy Frontiers in Immunology miRNA placental-derived natural killer cells ex vivo expansion anti-tumor cytolytic activity cellular immunotherapy |
| title | Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy |
| title_full | Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy |
| title_fullStr | Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy |
| title_full_unstemmed | Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy |
| title_short | Characterization and ex vivo Expansion of Human Placenta-Derived Natural Killer Cells for Cancer Immunotherapy |
| title_sort | characterization and ex vivo expansion of human placenta derived natural killer cells for cancer immunotherapy |
| topic | miRNA placental-derived natural killer cells ex vivo expansion anti-tumor cytolytic activity cellular immunotherapy |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00101/full |
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