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| Item Type: | Article |
|---|---|
| Title: | Quadruple gene-engineered natural killer cells enable multi-antigen targeting for durable antitumor activity against multiple myeloma |
| Creators Name: | Cichocki, F. and Bjordahl, R. and Goodridge, J.P. and Mahmood, S. and Gaidarova, S. and Abujarour, R. and Davis, Z.B. and Merino, A. and Tuininga, K. and Wang, H. and Kumar, A. and Groff, B. and Witty, A. and Bonello, G. and Huffman, J. and Dailey, T. and Lee, T.T. and Malmberg, K.J. and Walcheck, B. and Höpken, U. and Rehm, A. and Valamehr, B. and Miller, J.S. |
| Abstract: | Allogeneic natural killer (NK) cell adoptive transfer is a promising treatment for several cancers but is less effective for the treatment of multiple myeloma. In this study, we report on quadruple gene-engineered induced pluripotent stem cell (iPSC)-derived NK cells designed for mass production from a renewable source and for dual targeting against multiple myeloma through the introduction of an NK cell-optimized chimeric antigen receptor (CAR) specific for B cell maturation antigen (BCMA) and a high affinity, non-cleavable CD16 to augment antibody-dependent cellular cytotoxicity when combined with therapeutic anti-CD38 antibodies. Additionally, these cells express a membrane-bound interleukin-15 fusion molecule to enhance function and persistence along with knock out of CD38 to prevent antibody-mediated fratricide and enhance NK cell metabolic fitness. In various preclinical models, including xenogeneic adoptive transfer models, quadruple gene-engineered NK cells consistently demonstrate durable antitumor activity independent of exogenous cytokine support. Results presented here support clinical translation of this off-the-shelf strategy for effective treatment of multiple myeloma. |
| Keywords: | B-Cell Maturation Antigen, Multiple Myeloma, NK Cell Lectin-Like Receptor Subfamily D, Natural Killer Cell Receptors, Natural Killer Cells |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 7341 |
| Date: | 29 November 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-022-35127-2 |
| PubMed: | View item in PubMed |
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