Engineering Anti-Tumor Monoclonal Antibodies and Fc Receptors to Enhance ADCC by Human NK Cells.
Engineering Anti-Tumor Monoclonal Antibodies and Fc Receptors to Enhance ADCC by Human NK Cells.
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DOI：
10.3390/cancers13020312
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发表时间：
2021-01-16
期刊：
影响因子：
5.2
通讯作者：
Walcheck B
中科院分区：
文献类型：
--
作者：
Dixon KJ;Wu J;Walcheck B
人自然杀伤（NK）细胞可以通过其IgG Fc受体靶向肿瘤抗原，所述IgG Fc受体与识别癌细胞上的表面蛋白的抗体的Fc区相互作用。特异于癌细胞抗原的治疗性抗体用于治疗各种恶性肿瘤。NK细胞又通过称为抗体依赖性细胞介导的细胞毒性（ADCC）的过程杀死抗体结合的肿瘤细胞。NK细胞的ADCC应答可以通过抗体或Fc受体的变化来调节。在这篇综述中，我们详细介绍了Fc受体在人类NK细胞中的功能，并扩展了目前的研究，说明工程单克隆抗体和Fc受体如何增强NK细胞介导的ADCC治疗癌症。肿瘤靶向单克隆抗体（mAb）是血液肿瘤和实体瘤最广泛使用和表征的免疫疗法。这种疗法的意义在于它们分别通过抗体的抗原结合片段（Fab）和片段可结晶区（Fc区）促进对肿瘤细胞的直接和间接作用。Fab可以以激动或拮抗方式调节肿瘤细胞上细胞表面标志物的功能，而Fc区可以被白细胞上的Fc受体（FcR）识别，通过其可以引发各种效应子功能，包括抗体依赖性细胞介导的细胞毒性（ADCC）。该过程是自然杀伤（NK）细胞的关键细胞溶解机制。人体内的这些先天性淋巴细胞仅通过IgG Fc受体CD16A（FcγRIIIA）识别肿瘤结合抗体。CD16A的两个等位基因版本以较低或较高的亲和力结合IgG。据报道，CD16A的高亲和力等位基因纯合子的癌症患者对各种恶性肿瘤的mAb疗法的反应显著更好。这些研究揭示了mAb治疗功效与更高的与CD16A的亲和力结合正相关。通过修饰抗体的Fc部分或NK细胞上的FcR来增强NK细胞对肿瘤抗原的靶向性是本文的重点。
Human natural killer (NK) cells can be targeted to tumor antigens by their IgG Fc receptors that interact with the Fc regions of antibodies that recognize surface proteins on cancer cells. Therapeutic antibodies specific to cancer cell antigens are used to treat various malignancies. NK cells in turn kill antibody-bound tumor cells through a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). The ADCC response of NK cells can be modulated by changes in the antibody or Fc receptor. In this review, we detail the functions of Fc receptors in human NK cells and expand upon current research illustrating how engineering monoclonal antibodies and Fc receptors enhance NK cell-mediated ADCC for the treatment of cancer. Tumor-targeting monoclonal antibodies (mAbs) are the most widely used and characterized immunotherapy for hematologic and solid tumors. The significance of this therapy is their direct and indirect effects on tumor cells, facilitated by the antibody’s antigen-binding fragment (Fab) and fragment crystallizable region (Fc region), respectively. The Fab can modulate the function of cell surface markers on tumor cells in an agonistic or antagonistic manner, whereas the Fc region can be recognized by an Fc receptor (FcR) on leukocytes through which various effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), can be elicited. This process is a key cytolytic mechanism of natural killer (NK) cells. These innate lymphocytes in the human body recognize tumor-bound antibodies exclusively by the IgG Fc receptor CD16A (FcγRIIIA). Two allelic versions of CD16A bind IgG with either lower or higher affinity. Cancer patients homozygous for the higher affinity allele of CD16A have been reported to respond significantly better to mAb therapies for various malignancies. These studies revealed that mAb therapy efficacy positively correlates with higher affinity binding to CD16A. Approaches to enhance tumor antigen targeting by NK cells by modifying the Fc portion of antibodies or the FcR on NK cells are the focus of this review.
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影响因子：
3
作者：
Ahmed, Alysia A.;Keremane, Sravya R.;Bjorkman, Pamela J.
通讯作者：
Bjorkman, Pamela J.
在人类天然杀伤细胞中，活化T细胞NFATP和NFATC的核因子的激活和表达：CD16配体结合时调节。
DOI：
10.1084/jem.182.3.801
发表时间：
1995-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Aramburu J;Azzoni L;Rao A;Perussia B
通讯作者：
Perussia B
影响因子：
20.3
作者：
Bryceson, YT;March, ME;Long, EO
通讯作者：
Long, EO
影响因子：
11.5
作者：
Dolstra, Harry;Roeven, Mieke W. H.;Schaap, Nicolaas M.
通讯作者：
Schaap, Nicolaas M.
影响因子：
45.3
作者：
Bibeau, Frederic;Lopez-Crapez, Evelyne;Boissiere-Michot, Florence
通讯作者：
Boissiere-Michot, Florence