NKp44-based chimeric antigen receptor effectively redirects primary T cells against synovial sarcoma.
NKp44-based chimeric antigen receptor effectively redirects primary T cells against synovial sarcoma.
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DOI：
10.1016/j.tranon.2022.101521
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发表时间：
2022-11
影响因子：
5
通讯作者：
Imai, Chihaya
中科院分区：
文献类型：
--
作者：
Murayama, Yudai;Kasahara, Yasushi;Kubo, Nobuhiro;Shin, Chansu;Imamura, Masaru;Oike, Naoki;Ariizumi, Takashi;Saitoh, Akihiko;Baba, Minori;Miyazaki, Tomohiro;Suzuki, Yuko;Ling, Yiwei;Okuda, Shujiro;Mihara, Keichiro;Ogose, Akira;Kawashima, Hiroyuki;Imai, Chihaya
CAR-based细胞疗法可能是治疗滑膜肉瘤的一种选择。NKp44配体在滑膜肉瘤细胞中最为普遍。基于nkp44的CAR - T细胞产生大量的IFN-γ。基于nkp44的CAR - T细胞对滑膜肉瘤产生抗肿瘤作用。CAR可以将原代人T细胞转移到滑膜肉瘤细胞。在临床试验中，t细胞受体工程t细胞疗法在治疗滑膜肉瘤方面取得了良好的应答率，但由于HLA匹配要求，其适用性受到限制。嵌合抗原受体（CAR）可以在不需要HLA匹配的情况下将原代T细胞定向到肿瘤相关抗原。然而，各种障碍，包括缺乏靶向抗原，必须解决滑膜肉瘤。自然杀伤（NK）细胞激活受体的配体在肿瘤细胞中高度表达。分析了滑膜肉瘤细胞系中NK细胞活化受体配体的表面表达。我们分析了存储在公共数据库中的RNA测序数据，以评估nkp44配体的表达。用CAR靶向NKp44配体逆转录转导原代T细胞，评估其在滑膜肉瘤细胞中的功能。研究了各种刺激（包括组蛋白去乙酰化酶抑制剂、低甲基化剂、炎症细胞因子和电离辐射）对NKp44配体表达水平的影响。NKp44和NKp30的配体在所有细胞系中均有表达。NKG2D配体在单个细胞系中几乎不表达。没有细胞系表达NKp46配体。原代滑膜肉瘤细胞表达MLL5的截断异构体的mRNA， MLL5是一种已知的NKp44的细胞配体。基于nkp44的CAR - T细胞特异性识别滑膜肉瘤细胞，分泌干扰素-γ，对肿瘤细胞生长发挥抑制作用。没有刺激改变NKp44配体的表达。基于nkp44的CAR - T细胞可以将原代人T细胞重定向到滑膜肉瘤细胞。CAR-based细胞疗法可能是治疗滑膜肉瘤的一种选择。
CAR-based cell therapies may be an option for treating synovial sarcomas. NKp44 ligands were found to be most prevalent in synovial sarcoma cells. NKp44-based CAR T cells produced significantly amounts of IFN-γ. NKp44-based CAR T cells produced antitumor effects against synovial sarcomas. CAR can redirect primary human T cells to synovial sarcoma cells. T-cell receptor-engineered T-cell therapies have achieved promising response rates against synovial sarcoma in clinical trials, but their applicability is limited owing to the HLA matching requirement. Chimeric antigen receptor (CAR) can redirect primary T cells to tumor-associated antigens without requiring HLA matching. However, various obstacles, including the paucity of targetable antigens, must be addressed for synovial sarcoma. Ligands for natural killer (NK) cell-activating receptors are highly expressed by tumor cells. The surface expression of ligands for NK cell-activating receptors in synovial sarcoma cell lines was analyzed. We analyzed RNA sequencing data deposited in a public database to evaluate NKp44-ligand expression. Primary T cells retrovirally transduced with CAR targeting NKp44 ligands were evaluated for their functions in synovial sarcoma cells. Alterations induced by various stimuli, including a histone deacetylase inhibitor, a hypomethylating agent, inflammatory cytokines, and ionizing radiation, in the expression levels of NKp44 ligands were investigated. : Ligands for NKp44 and NKp30 were expressed in all cell lines. NKG2D ligands were barely expressed in a single cell line. None of the cell lines expressed NKp46 ligand. Primary synovial sarcoma cells expressed the mRNA of the truncated isoform of MLL5, a known cellular ligand for NKp44. NKp44-based CAR T cells specifically recognize synovial sarcoma cells, secrete interferon-γ, and exert suppressive effects on tumor cell growth. No stimulus altered the expression of NKp44 ligands. NKp44-based CAR T cells can redirect primary human T cells to synovial sarcoma cells. CAR-based cell therapies may be an option for treating synovial sarcomas.
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影响因子：
9.3
作者：
Savina M;Le Cesne A;Blay JY;Ray-Coquard I;Mir O;Toulmonde M;Cousin S;Terrier P;Ranchere-Vince D;Meeus P;Stoeckle E;Honoré C;Sargos P;Sunyach MP;Le Péchoux C;Giraud A;Bellera C;Le Loarer F;Italiano A
通讯作者：
Italiano A
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
28.2
作者：
D'Angelo SP;Melchiori L;Merchant MS;Bernstein D;Glod J;Kaplan R;Grupp S;Tap WD;Chagin K;Binder GK;Basu S;Lowther DE;Wang R;Bath N;Tipping A;Betts G;Ramachandran I;Navenot JM;Zhang H;Wells DK;Van Winkle E;Kari G;Trivedi T;Holdich T;Pandite L;Amado R;Mackall CL
通讯作者：
Mackall CL
影响因子：
16.6
作者：
Hegde, Meenakshi;Joseph, Sujith K.;Ahmed, Nabil
通讯作者：
Ahmed, Nabil
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen