Other
17 Authors
- Yi J,
- Mansour AG,
- Teng KY,
- Li Z,
- Kollath DS,
- Zhang J,
- Yu J,
- Caligiuri MA,
- Keim PS,
- Tian L,
- Lu T,
- Dong W,
- Bustillos C,
- Ma R,
- Barker BM,
- Ma S,
- Settles EW
| First Author | Lu T | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 2576 |
| PubMed ID | 35546150 | Mgi Jnum | J:335944 |
| Mgi Id | MGI:7280246 | Doi | 10.1038/s41467-022-30216-8 |
| Citation | Lu T, et al. (2022) Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19. Nat Commun 13(1):2576 |
| abstractText | Engineered natural killer (NK) cells represent a promising option for immune therapy option due to their immediate availability in allogeneic settings. Severe acute diseases, such as COVID-19, require targeted and immediate intervention. Here we show engineering of NK cells to express (1) soluble interleukin-15 (sIL15) for enhancing their survival and (2) a chimeric antigen receptor (CAR) consisting of an extracellular domain of ACE2, targeting the spike protein of SARS-CoV-2. These CAR NK cells (mACE2-CAR_sIL15 NK cells) bind to VSV-SARS-CoV-2 chimeric viral particles as well as the recombinant SARS-CoV-2 spike protein subunit S1 leading to enhanced NK cell production of TNF-alpha and IFN-gamma and increased in vitro and in vivo cytotoxicity against cells expressing the spike protein. Administration of mACE2-CAR_sIL15 NK cells maintains body weight, reduces viral load, and prolongs survival of transgenic mice expressing human ACE2 upon infection with live SARS-CoV-2. These experiments, and the capacity of mACE2-CAR_sIL15 NK cells to retain their activity following cryopreservation, demonstrate their potential as an allogeneic off-the-shelf therapy for COVID-19 patients who are faced with limited treatment options. |
