Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo
Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated clinical success in treatment of B-cell hematologic cancers. In this study, we compared human Transferrin epitope tagged CAR-T cells with non-tagged CAR-T cells for cytotoxicity, IFN-gamma secretion and tumor clearance in NSG mice...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2020-01-01
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| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/25/2/10.2741/4806 |
| _version_ | 1811306070847520768 |
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| author | Michael Valentine Le Li Hua Zhou Shirley Xu Jinying Sun Chengjing Liu Hizkia Harto Robert Berahovich Vita Golubovskaya Lijun Wu |
| author_facet | Michael Valentine Le Li Hua Zhou Shirley Xu Jinying Sun Chengjing Liu Hizkia Harto Robert Berahovich Vita Golubovskaya Lijun Wu |
| author_sort | Michael Valentine |
| collection | DOAJ |
| description | Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated clinical success in treatment of B-cell hematologic cancers. In this study, we compared human Transferrin epitope tagged CAR-T cells with non-tagged CAR-T cells for cytotoxicity, IFN-gamma secretion and tumor clearance in NSG mice. CD19-TF-CAR-T cells had similar cytotoxicity in vitro to CD19-CAR-T cells against cells expressing CD19 antigen: exogenously CD19+ Hela cells and endogenously CD19+ Raji cells. In addition, CD22-TF CAR-T cells were similarly cytotoxic against CD22+ CHO cells and CD22+ Raji cells. Both CD19-TF or CD22-TF-CAR-T cells secreted less IFN-gamma as compared to non-tagged CAR-T cells. In a Raji xenograft NSG mouse model, CD19-TF-CAR-T cells were as effective as CD19-CAR-T cells in reducing tumor growth and extending mouse survival. The results show that CD19-TF-CAR-T cells can be monitored using TF antibody in vitro and ex vivo, and that these cells effectively killed Raji cells in vitro and in vivo with reduced secretion of IFN-gamma. Thus, these TF-tagged CAR-T cells might have improved safety and provide a basis for future clinical studies. |
| first_indexed | 2024-04-13T08:37:48Z |
| format | Article |
| id | doaj.art-687fefd540d744319cd8c15256868f67 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-13T08:37:48Z |
| publishDate | 2020-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-687fefd540d744319cd8c15256868f672022-12-22T02:54:01ZengIMR PressFrontiers in Bioscience-Landmark2768-67012020-01-0125227028210.2741/4806FBS-25-270Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivoMichael Valentine0Le Li1Hua Zhou2Shirley Xu3Jinying Sun4Chengjing Liu5Hizkia Harto6Robert Berahovich7Vita Golubovskaya8Lijun Wu9ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated clinical success in treatment of B-cell hematologic cancers. In this study, we compared human Transferrin epitope tagged CAR-T cells with non-tagged CAR-T cells for cytotoxicity, IFN-gamma secretion and tumor clearance in NSG mice. CD19-TF-CAR-T cells had similar cytotoxicity in vitro to CD19-CAR-T cells against cells expressing CD19 antigen: exogenously CD19+ Hela cells and endogenously CD19+ Raji cells. In addition, CD22-TF CAR-T cells were similarly cytotoxic against CD22+ CHO cells and CD22+ Raji cells. Both CD19-TF or CD22-TF-CAR-T cells secreted less IFN-gamma as compared to non-tagged CAR-T cells. In a Raji xenograft NSG mouse model, CD19-TF-CAR-T cells were as effective as CD19-CAR-T cells in reducing tumor growth and extending mouse survival. The results show that CD19-TF-CAR-T cells can be monitored using TF antibody in vitro and ex vivo, and that these cells effectively killed Raji cells in vitro and in vivo with reduced secretion of IFN-gamma. Thus, these TF-tagged CAR-T cells might have improved safety and provide a basis for future clinical studies.https://www.imrpress.com/journal/FBL/25/2/10.2741/4806chimeric antigen receptorimmunotherapyepitopetransferrincd19cd22 |
| spellingShingle | Michael Valentine Le Li Hua Zhou Shirley Xu Jinying Sun Chengjing Liu Hizkia Harto Robert Berahovich Vita Golubovskaya Lijun Wu Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo Frontiers in Bioscience-Landmark chimeric antigen receptor immunotherapy epitope transferrin cd19 cd22 |
| title | Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo |
| title_full | Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo |
| title_fullStr | Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo |
| title_full_unstemmed | Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo |
| title_short | Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo |
| title_sort | transferrin epitope cd19 car t cells effectively kill lymphoma cells in vitro and in vivo |
| topic | chimeric antigen receptor immunotherapy epitope transferrin cd19 cd22 |
| url | https://www.imrpress.com/journal/FBL/25/2/10.2741/4806 |
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