Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells
Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colo...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/238924 |
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| author | Claudia Schlimper Andreas A. Hombach Hinrich Abken Ingo G. H. Schmidt-Wolf |
| author_facet | Claudia Schlimper Andreas A. Hombach Hinrich Abken Ingo G. H. Schmidt-Wolf |
| author_sort | Claudia Schlimper |
| collection | DOAJ |
| description | Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions. |
| format | Article |
| id | doaj-art-080f9e84f3cb4fdeb0605f45e99e5eac |
| institution | OA Journals |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-080f9e84f3cb4fdeb0605f45e99e5eac2025-08-20T02:01:39ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/238924238924Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer CellsClaudia Schlimper0Andreas A. Hombach1Hinrich Abken2Ingo G. H. Schmidt-Wolf3Department of Neurosurgery, University of Bonn, 53127 Bonn, GermanyCenter for Molecular Medicine Cologne and Department I of Internal Medicine, University of Cologne, 53901 Cologne, GermanyCenter for Molecular Medicine Cologne and Department I of Internal Medicine, University of Cologne, 53901 Cologne, GermanyCenter for Integrated Oncology Cologne-Bonn, GermanyAdoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.http://dx.doi.org/10.1155/2012/238924 |
| spellingShingle | Claudia Schlimper Andreas A. Hombach Hinrich Abken Ingo G. H. Schmidt-Wolf Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells Clinical and Developmental Immunology |
| title | Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells |
| title_full | Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells |
| title_fullStr | Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells |
| title_full_unstemmed | Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells |
| title_short | Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells |
| title_sort | improved activation toward primary colorectal cancer cells by antigen specific targeting autologous cytokine induced killer cells |
| url | http://dx.doi.org/10.1155/2012/238924 |
| work_keys_str_mv | AT claudiaschlimper improvedactivationtowardprimarycolorectalcancercellsbyantigenspecifictargetingautologouscytokineinducedkillercells AT andreasahombach improvedactivationtowardprimarycolorectalcancercellsbyantigenspecifictargetingautologouscytokineinducedkillercells AT hinrichabken improvedactivationtowardprimarycolorectalcancercellsbyantigenspecifictargetingautologouscytokineinducedkillercells AT ingoghschmidtwolf improvedactivationtowardprimarycolorectalcancercellsbyantigenspecifictargetingautologouscytokineinducedkillercells |