不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Novel anti-ITGA4 monoclonal antibody induces cell death via large pore formation in NK/T-cell lymphoma cells.
Novel anti-ITGA4 monoclonal antibody induces cell death via large pore formation in NK/T-cell lymphoma cells.
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自然杀伤(NK)/T细胞淋巴瘤是一种高度侵袭性的淋巴瘤亚型,常见于东亚和拉丁美洲。为开发针对该病的治疗性单克隆抗体(mAb),用两种强效NK淋巴瘤细胞系交替免疫BALB/c小鼠。杂交后,将杂交瘤克隆的培养上清液加入未用于免疫的第三种NK淋巴瘤细胞系,筛选具有直接溶细胞活性的抗体。结果显示,新建立的mAb命名为mAb ANAP,以细胞骨架依赖的方式诱导NK淋巴瘤细胞即刻死亡,该过程也不依赖补体、抗体依赖性细胞介导的细胞毒作用及caspase,在20 min内于靶细胞表面形成大孔;mAb ANAP不损伤正常细胞,并能结合ITGA4(CD49d)。与现有抗ITGA4抗体对NK淋巴瘤不表现任何破坏活性相反,ANAP抗体作为NK淋巴瘤治疗药物具有广阔前景。
Natural killer (NK)/T-cell lymphomas are a highly aggressive lymphoma subtype common in East Asia and Latin America. To develop a therapeutic monoclonal antibody (mAb) against it, BALB/c mice were alternately immunized with two vigorous NK lymphoma cell lines. After hybridization, culture supernatants of the hybridoma clones were added to a third NK lymphoma cell line not used for immunization, and the antibodies were screened for direct cytolytic activity.
Results showed that the newly established mAb, named mAb ANAP, induced immediate cell death against NK lymphoma cells in a cytoskeleton-dependent manner, which was also complement-, antibody-dependent cell-mediated cytotoxicity-, and caspase-independent, forming large pores on target cell surface within 20 min; mAb ANAP did not injure normal cells and could bind to the ITGA4 (CD49d).
Contrary to existing anti-ITGA4 antibodies, which did not exhibit any destructive activity against NK lymphoma, ANAP antibody has promising potential as a therapeutic agent for NK lymphoma.
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