Ollier Jocelyn, Vivien Régine, Vié Henri, Clémenceau Béatrice
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes 44007, France.
Etablissement Français du Sang, Pays de la Loire, Site de Nantes, Nantes 44000, France.
Immunohorizons. 2017 Jul 14;1(5):63-70. doi: 10.4049/immunohorizons.1700022. Print 2017 Jul 1.
To combine the immune potential of T cells and Ab therapy, we and others have previously shown that T cells transduction with a fusion receptor that binds the Fc portion of human Ig enable them to mediate Ab-dependent cellular cytotoxicity (ADCC). The fusion receptors previously described included the FcγRIIIa (CD16) receptor coupled to different chains intended to translate the signal. In this work, we questioned whether the transfection of CD16 alone into T human lymphocytes and NK cells could be sufficient for CD16 expression and function, or whether the cotransfection of a transducing chain was mandatory. Our results demonstrated that: 1) transfection of CD16 alone into a human NK cell line and primary T cells can be sufficient for CD16 expression and function; 2) cotransfection of CD3ζ or FcεRIγ increased CD16 expression; 3) yet this increased CD16 expression increased the ADCC score only for trastuzumab, not for rituximab or cetuximab; and 4) compared with that of peripheral NK cells, ADCC scores by autologous CD16-transfected T cells ranked differently according to the opsonized target cell. Together, these results showed that neither the use of a fusion receptor nor the cotransfection of a transducing chain is mandatory to transfer the ADCC function to human lymphocytes. Thus, depending on the effector/Ab/target combination considered, transfection of CD16 alone can be sufficient to enable T cells to mediate ADCC. In the context of immunotherapy, such a strategy is by nature safer than the use of a chimeric receptor, and is freely available.
为了结合T细胞的免疫潜力和抗体疗法，我们和其他研究人员先前已经表明，用结合人Ig Fc部分的融合受体转导T细胞能够使其介导抗体依赖性细胞毒性（ADCC）。先前描述的融合受体包括与不同链偶联的FcγRIIIa（CD16）受体，旨在转导信号。在这项研究中，我们质疑单独将CD16转染到人T淋巴细胞和NK细胞中是否足以实现CD16的表达和功能，或者转导链的共转染是否是必需的。我们的结果表明：1）将CD16单独转染到人NK细胞系和原代T细胞中足以实现CD16的表达和功能；2）共转染CD3ζ或FcεRIγ可增加CD16的表达；3）然而，这种增加的CD16表达仅增加了曲妥珠单抗的ADCC评分，而对利妥昔单抗或西妥昔单抗则没有增加；4）与外周NK细胞相比，自体CD16转染的T细胞的ADCC评分根据调理的靶细胞不同而排名不同。总之，这些结果表明，将ADCC功能转移到人淋巴细胞中，既不需要使用融合受体，也不需要共转染转导链。因此，根据所考虑的效应细胞/抗体/靶细胞组合，单独转染CD16就足以使T细胞介导ADCC。在免疫治疗的背景下，这种策略本质上比使用嵌合受体更安全，并且是免费可用的。
