天然杀伤细胞与天然细胞接合物预复合的冷冻保存

IF 3 Q3 IMMUNOLOGY Antibodies Pub Date : 2022-02-09 DOI:10.3390/antib11010012
U. Reusch, Kristina Ellwanger, Ivica Fucek, Thomas Müller, Ute Schniegler-Mattox, J. Koch, M. Tesar
{"title":"天然杀伤细胞与天然细胞接合物预复合的冷冻保存","authors":"U. Reusch, Kristina Ellwanger, Ivica Fucek, Thomas Müller, Ute Schniegler-Mattox, J. Koch, M. Tesar","doi":"10.3390/antib11010012","DOIUrl":null,"url":null,"abstract":"Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE® constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE® antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE® construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE® complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE® drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers\",\"authors\":\"U. Reusch, Kristina Ellwanger, Ivica Fucek, Thomas Müller, Ute Schniegler-Mattox, J. Koch, M. Tesar\",\"doi\":\"10.3390/antib11010012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE® constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE® antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE® construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE® complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE® drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells.\",\"PeriodicalId\":8188,\"journal\":{\"name\":\"Antibodies\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2022-02-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antibodies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/antib11010012\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antibodies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/antib11010012","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 3

摘要

先天性细胞接合器(ICE®)构建物是针对特定肿瘤抗原的双特异性四价抗体,同时结合自然杀伤细胞(NK)和巨噬细胞受体来破坏肿瘤细胞。ICE®构建物与过继NK细胞的预络合是一种增强NK细胞活性的新方法。这种复合物适合冷冻保存,同时保留生物活性和特异性,可能使开发现成的NK细胞产品成为可能。本研究探讨了针对EpCAM和NK细胞受体CD16A、NKG2D或NKp46的ICE®构建物与相应抗原的结合亲和力、ICE®抗肿瘤活性以及冷冻保存的可行性。使用原代NK细胞进行的细胞表面保留试验证实,与对照分子相比,ICE®构建的解离动力学要慢得多,这表明ICE®构建的持久复合物的形成独立于CD16A多态性。高亲和力NK细胞和EpCAM/CD16A ICE®复合物在NK细胞介导的EpCAM表达肿瘤细胞的消除测试中优于NKG2D或NKp46受体。此外,这些复合物的效力和功效在单次冻融循环后不受影响。cd16a选择性ICE®候选药物与NK细胞复合物有望成为新型冷冻保存的现成NK细胞产品,具有嵌合抗原受体样NK细胞特性,能够有效地消耗肿瘤细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers
Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE® constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE® antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE® construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE® complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE® drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Antibodies
Antibodies IMMUNOLOGY-
CiteScore
7.10
自引率
6.40%
发文量
68
审稿时长
11 weeks
期刊介绍: Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.
期刊最新文献
Oral Paraneoplastic Pemphigus: A Scoping Review on Pathogenetic Mechanisms and Histo-Serological Profile. Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model. Generation, Characterization, and Preclinical Studies of a Novel NKG2A-Targeted Antibody BRY805 for Cancer Immunotherapy. High Prevalence of aCL-IgA and aβ2GPI-IgA in Drug-Free Schizophrenia Patients: Evidence of a Potential Autoimmune Link. Ocular Mucous Membrane Pemphigoid Demonstrates a Distinct Autoantibody Profile from Those of Other Autoimmune Blistering Diseases: A Preliminary Study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1