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| Item Type: | Article |
|---|---|
| Title: | Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma |
| Creators Name: | Seidel, D., Shibina, A., Siebert, N., Wels, W.S., Reynolds, C.P., Huebener, N. and Lode, H.N. |
| Abstract: | The disialoganglioside GD2 is a well-established target antigen for passive immunotherapy in neuroblastoma (NB). Despite the recent success of passive immunotherapy with the anti-GD2 antibody ch14.18 and cytokines, treatment of high-risk NB remains challenging. We expanded the approach of GD2-specific, antibody-based immunotherapy to an application of a GD2-specific natural killer (NK) cell line, NK-92-scFv(ch14.18)-zeta. NK-92-scFv(ch14.18)-zeta is genetically engineered to express a GD2-specific chimeric antigen receptor generated from ch14.18. Here, we show that chimeric receptor expression enables NK-92-scFv(ch14.18)-zeta to effectively lyse GD2(+) NB cells also including partially or multidrug-resistant lines. Our data suggest that recognition of GD2 by the chimeric receptor is the primary mechanism involved in NK-92-scFv(ch14.18)-zeta-mediated lysis and is independent of activating NK cell receptor/ligand interactions. Furthermore, we demonstrate that NK-92-scFv(ch14.18)-zeta is able to mediate a significant anti-tumor response in vivo in a drug-resistant GD2(+) NB xenograft mouse model. NK-92-scFv(ch14.18)-zeta is an NB-specific NK cell line that has potential for future clinical development due to its high stability and activity toward GD2(+) NB cell lines. |
| Keywords: | Neuroblastoma GD2, Chimeric Antigen Receptor, Natural Killer Cell, Single-Chain Antibody |
| Source: | Cancer Immunology Immunotherapy |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Volume: | 64 |
| Number: | 5 |
| Page Range: | 621-634 |
| Date: | May 2015 |
| Official Publication: | https://doi.org/10.1007/s00262-015-1669-5 |
| PubMed: | View item in PubMed |
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