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Improved Activity against Acute Myeloid Leukemia with Chimeric Antigen Receptor (CAR)-NK-92 Cells Designed to Target CD123
| Content Provider | MDPI |
|---|---|
| Author | Morgan, Michael Kloos, Arnold Lenz, Daniela Kattre, Nadine Nowak, Juliette Bentele, Marco Keisker, Maximilian Dahlke, Julia Zimmermann, Katharina Sauer, Martin Heuser, Michael Schambach, Axel |
| Copyright Year | 2021 |
| Description | Anti-cancer activity can be improved by engineering immune cells to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens. Retroviral vector gene transfer strategies allow stable and durable transgene expression. Here, we used alpharetroviral vectors to modify NK-92 cells, a natural killer cell line, with a third-generation CAR designed to target the IL-3 receptor subunit alpha (CD123), which is strongly expressed on the surface of acute myeloid leukemia (AML) cells. Alpharetroviral vectors also contained a transgene cassette to allow constitutive expression of human IL-15 for increased NK cell persistence in vivo. The anti-AML activity of CAR-NK-92 cells was tested via in vitro cytotoxicity assays with the $CD123^{+}$ AML cell line KG-1a and in vivo in a patient-derived xenotransplantation $CD123^{+}$ AML model. Unmodified NK-92 cells or NK-92 cells modified with a truncated version of the CAR that lacked the signaling domain served as controls. Alpharetroviral vector-modified NK-92 cells stably expressed the transgenes and secreted IL-15. Anti-CD123-CAR-NK-92 cells exhibited enhanced anti-AML activity in vitro and in vivo as compared to control NK-92 cells. Our data (1) shows the importance of IL-15 expression for in vivo persistence of NK-92 cells, (2) supports continued investigation of anti-CD123-CAR-NK cells to target AML, and (3) points towards potential strategies to further improve CAR-NK anti-AML activity. |
| Starting Page | 1365 |
| e-ISSN | 19994915 |
| DOI | 10.3390/v13071365 |
| Journal | Viruses |
| Issue Number | 7 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-07-14 |
| Access Restriction | Open |
| Subject Keyword | Viruses Oncology Alpharetroviral Vector Acute Myeloid Leukemia Chimeric Antigen Receptor Cd123 Interleukin 3 Receptor Subunit Alpha Patient-derived Xenograft Il-15 Nk-92 |
| Content Type | Text |
| Resource Type | Article |
