Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.
Antigen Presentation & T/NK Cell Unit, Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Int Immunopharmacol. 2021 Jul;96:107762. doi: 10.1016/j.intimp.2021.107762. Epub 2021 May 31.
Cancer/tumor cells infected with the "avian paramyxovirus Newcastle Disease Virus (TC-NDV)" express the viral hemagglutinin-neuraminidase (HN) on the cell surface that is used as both the danger signal and anchor for bi/tri-specific antibodies (bs/tsAbs).We constructed a bs-Ab (HN-Fc-CD16) that bindsto HN and natural killer (NK)-CD16 receptor (FcgRIII)and a ts-Ab (HN-Fc-IL15-CD16) harbouring NK-activating cytokine "IL-15" within the bs-Ab.In silicoand computational predictions indicated proper exposure of both Abs in bs/tsAbs.Properbinding of thebi/tsAbstoHN on surface of TC-NDVandCD16-cells was demonstrated by flow cytometry.The bi/tsAbstriggeredspecificcytotoxicity of NK cells againstTC-NDVand elicited substantial IFN-γproduction by activated NK cells(higher for ts-Ab) that sound promising for cancer immunotherapy purposes.
受“禽副黏病毒新城疫病毒（TC-NDV）”感染的癌细胞/肿瘤细胞在细胞表面表达病毒血凝素-神经氨酸酶（HN），该蛋白既可用作危险信号，也可用作双特异性/三特异性抗体（bs/tsAbs）的锚点。我们构建了一种 bs-Ab（HN-Fc-CD16），它与 HN 和自然杀伤（NK）-CD16 受体（FcgRIII）结合，另一种 ts-Ab（HN-Fc-IL15-CD16）则在 bs-Ab 内携带 NK 激活细胞因子“IL-15”。计算机预测表明 bs/tsAbs 中两种抗体均能正确暴露。通过流式细胞术证实了 bs/tsAb 对 TC-NDV 和 CD16 细胞表面上的 HN 的适当结合。bi/tsAb 可触发 NK 细胞对 TC-NDV 的特异性细胞毒性，并诱导活化的 NK 细胞产生大量 IFN-γ（ts-Ab 更高），这对癌症免疫治疗具有重要意义。
