Matches in SemOpenAlex for { <https://semopenalex.org/work/W4288447006> ?p ?o ?g. }
- W4288447006 abstract "Adoptive transfer of engineered NK cells, one of clinical approaches to fight cancer, is gaining great interest in the last decade. However, the development of new strategies is needed to improve clinical efficacy and safety of NK cell-based immunotherapy. NK cell-mediated recognition and lysis of tumor cells are strictly dependent on the expression of ligands for NK cell-activating receptors NKG2D and DNAM-1 on tumor cells. Of note, the PVR/CD155 and Nectin-2/CD112 ligands for DNAM-1 are expressed primarily on solid tumor cells and poorly expressed in normal tissue cells. Here, we generated human NK cells expressing either the full length DNAM-1 receptor or three different DNAM-1-based chimeric receptor that provide the expression of DNAM-1 fused to a costimulatory molecule such as 2B4 and CD3ζ chain. Upon transfection into primary human NK cells isolated from healthy donors, we evaluated the surface expression of DNAM-1 and, as a functional readout, we assessed the extent of degranulation, cytotoxicity and the production of IFNγ and TNFα in response to human leukemic K562 cell line. In addition, we explored the effect of Nutlin-3a, a MDM2-targeting drug able of restoring p53 functions and known to have an immunomodulatory effect, on the degranulation of DNAM-1-engineered NK cells in response to human neuroblastoma (NB) LA-N-5 and SMS-KCNR cell lines. By comparing NK cells transfected with four different plasmid vectors and through blocking experiments, DNAM-1-CD3ζ-engineered NK cells showed the strongest response. Furthermore, both LA-N-5 and SMS-KCNR cells pretreated with Nutlin-3a were significantly more susceptible to DNAM-1-engineered NK cells than NK cells transfected with the empty vector. Our results provide a proof-of-concept suggesting that the combined use of DNAM-1-chimeric receptor-engineered NK cells and Nutlin-3a may represent a novel therapeutic approach for the treatment of solid tumors, such as NB, carrying dysfunctional p53." @default.
- W4288447006 created "2022-07-29" @default.
- W4288447006 creator A5006383579 @default.
- W4288447006 creator A5026539734 @default.
- W4288447006 creator A5028319453 @default.
- W4288447006 creator A5029625572 @default.
- W4288447006 creator A5048387531 @default.
- W4288447006 creator A5050257455 @default.
- W4288447006 creator A5054917672 @default.
- W4288447006 creator A5058147481 @default.
- W4288447006 creator A5073130754 @default.
- W4288447006 creator A5073730516 @default.
- W4288447006 creator A5086171339 @default.
- W4288447006 date "2022-07-28" @default.
- W4288447006 modified "2023-10-01" @default.
- W4288447006 title "DNAM-1-chimeric receptor-engineered NK cells, combined with Nutlin-3a, more effectively fight neuroblastoma cells in vitro: a proof-of-concept study" @default.
- W4288447006 cites W127707871 @default.
- W4288447006 cites W1789648125 @default.
- W4288447006 cites W1954860593 @default.
- W4288447006 cites W1967846044 @default.
- W4288447006 cites W1992947288 @default.
- W4288447006 cites W1993596892 @default.
- W4288447006 cites W1996717063 @default.
- W4288447006 cites W2000070744 @default.
- W4288447006 cites W2005203470 @default.
- W4288447006 cites W2014997010 @default.
- W4288447006 cites W2020181553 @default.
- W4288447006 cites W2020646453 @default.
- W4288447006 cites W2023283620 @default.
- W4288447006 cites W2034558707 @default.
- W4288447006 cites W2050752994 @default.
- W4288447006 cites W2052502668 @default.
- W4288447006 cites W2058522060 @default.
- W4288447006 cites W2060439989 @default.
- W4288447006 cites W2081228087 @default.
- W4288447006 cites W2083616674 @default.
- W4288447006 cites W2085478834 @default.
- W4288447006 cites W2097933346 @default.
- W4288447006 cites W2098930452 @default.
- W4288447006 cites W2099126386 @default.
- W4288447006 cites W2104192569 @default.
- W4288447006 cites W2120344463 @default.
- W4288447006 cites W2123143632 @default.
- W4288447006 cites W2124416339 @default.
- W4288447006 cites W2124637769 @default.
- W4288447006 cites W2130925781 @default.
- W4288447006 cites W2132151003 @default.
- W4288447006 cites W2144201925 @default.
- W4288447006 cites W2144436556 @default.
- W4288447006 cites W2149312162 @default.
- W4288447006 cites W2154518608 @default.
- W4288447006 cites W2160520392 @default.
- W4288447006 cites W2161379087 @default.
- W4288447006 cites W2170461079 @default.
- W4288447006 cites W2176019912 @default.
- W4288447006 cites W2201929875 @default.
- W4288447006 cites W2515812752 @default.
- W4288447006 cites W2605656134 @default.
- W4288447006 cites W2622456183 @default.
- W4288447006 cites W2737469573 @default.
- W4288447006 cites W2762253884 @default.
- W4288447006 cites W2767867771 @default.
- W4288447006 cites W2786453908 @default.
- W4288447006 cites W2794927343 @default.
- W4288447006 cites W2802646364 @default.
- W4288447006 cites W2808601843 @default.
- W4288447006 cites W2810715813 @default.
- W4288447006 cites W2902856530 @default.
- W4288447006 cites W2914155390 @default.
- W4288447006 cites W2914849333 @default.
- W4288447006 cites W2921636994 @default.
- W4288447006 cites W2922879840 @default.
- W4288447006 cites W2946995077 @default.
- W4288447006 cites W2947017746 @default.
- W4288447006 cites W2948485623 @default.
- W4288447006 cites W2966688037 @default.
- W4288447006 cites W2968221494 @default.
- W4288447006 cites W3001496296 @default.
- W4288447006 cites W3004130920 @default.
- W4288447006 cites W3006483160 @default.
- W4288447006 cites W3016574361 @default.
- W4288447006 cites W3022955468 @default.
- W4288447006 cites W3038967738 @default.
- W4288447006 cites W3041979963 @default.
- W4288447006 cites W3046244298 @default.
- W4288447006 cites W3080714131 @default.
- W4288447006 cites W3096190085 @default.
- W4288447006 cites W3112097879 @default.
- W4288447006 cites W3119838003 @default.
- W4288447006 cites W3157831753 @default.
- W4288447006 cites W3170965404 @default.
- W4288447006 cites W3194618061 @default.
- W4288447006 cites W3197645592 @default.
- W4288447006 cites W3198558595 @default.
- W4288447006 cites W3208140860 @default.
- W4288447006 cites W4200307569 @default.
- W4288447006 cites W4225265544 @default.
- W4288447006 cites W4255684672 @default.
- W4288447006 doi "https://doi.org/10.3389/fimmu.2022.886319" @default.
- W4288447006 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35967339" @default.