CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer.
Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer.
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自然杀伤(NK)细胞因其泛特异性靶点识别能力,在多种癌症中展现出巨大的治疗潜力。大量报道表明,NK细胞免疫治疗是治疗血液系统恶性肿瘤的有效方法,但对实体瘤效果有限。本研究采用多种卵巢癌(OC)模型,检测了来源于人外周血单个核细胞、并使用无饲养层细胞扩增系统扩增的NK细胞(eNKs)的抗癌效果。结果表明,eNKs在不同卵巢癌异种移植小鼠模型(即实体瘤、腹部转移瘤和腹水)中对肿瘤生长表现出强效抑制作用,重要的是,这种作用呈剂量依赖性。此外,过继转移eNKs可显著减少OC腹膜肿瘤模型中的腹水形成,尤其是在减少腹腔内腹水方面。我们发现,eNKs能够迁移至肿瘤部位,保持其活性,并增殖以在皮肤异种移植小鼠中维持高细胞数量。此外,当以12 10 7个细胞/小鼠的高剂量增加输注时,eNK可诱导移植物抗宿主病。这些数据表明,eNK细胞免疫治疗可能是卵巢癌(包括实体瘤和腹水)的一种有前景的治疗策略。
Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors.
In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i. e. , solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner.
Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites.
We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice.
In addition, when increased the infusion with a high dose of 12 10 7 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.
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