Human antibodies targeting ENPP1 as candidate therapeutics for cancers.
Human antibodies targeting ENPP1 as candidate therapeutics for cancers.
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靶向ENPP 1的人抗体作为癌症的候选治疗剂。
DOI：
10.3389/fimmu.2023.1070492
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发表时间：
2023
影响因子：
7.3
通讯作者：
Dimitrov, Dimiter S.
中科院分区：
文献类型：
--
作者：
Chu, Xiaojie;Baek, Du-San;Li, Wei;Shyp, Taras;Mooney, Brian;Hines, Margaret G.;Morin, Gregg B.;Sorensen, Poul H.;Dimitrov, Dimiter S.
关键词：
外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP 1）是一种II型跨膜糖蛋白，在许多组织中表达。在许多癌症类型如肺癌、卵巢癌和乳腺癌中已经观察到ENPP 1的高表达水平。这种过度表达与这些疾病的不良预后有关。因此，ENPP 1是多种癌症免疫治疗的潜在靶点。在这里，我们分离和表征两个高亲和力和特异性的抗ENPP 1 Fab抗体候选物，17和3G 12，从大的噬菌体展示的人Fab库。转化为IgG 1后，由于亲合力效应，两种抗体的结合显著增加。基于这些抗体，我们产生了抗体-药物缀合物（ADC）、基于IgG的双特异性T细胞增殖剂（IbTE）和CAR T细胞，它们都表现出对ENPP 1表达细胞的强效杀伤。因此，这些不同的抗体衍生形式是表达人ENPP 1的癌症的有希望的治疗候选物。
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with poor prognosis in these diseases. Hence, ENPP1 is a potential target for immunotherapy across multiple cancers. Here, we isolated and characterized two high-affinity and specific anti-ENPP1 Fab antibody candidates, 17 and 3G12, from large phage-displayed human Fab libraries. After conversion to IgG1, the binding of both antibodies increased significantly due to avidity effects. Based on these antibodies, we generated antibody-drug conjugates (ADCs), IgG-based bispecific T-cell engagers (IbTEs), and CAR T-cells which all exhibited potent killing of ENPP1-expressing cells. Thus, these various antibody-derived modalities are promising therapeutic candidates for cancers expressing human ENPP1.
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影响因子：
3.7
作者：
Di Paola R;Caporarello N;Marucci A;Dimatteo C;Iadicicco C;Del Guerra S;Prudente S;Sudano D;Miele C;Parrino C;Piro S;Beguinot F;Marchetti P;Trischitta V;Frittitta L
通讯作者：
Frittitta L
影响因子：
2.2
作者：
Chung, Shan;Lin, Yuwen L.;Song, An
通讯作者：
Song, An
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen
激动剂作为癌症治疗剂。
影响因子：
5.2
作者：
Amouzegar A;Chelvanambi M;Filderman JN;Storkus WJ;Luke JJ
通讯作者：
Luke JJ
DOI：
10.1016/j.jbc.2021.100966
发表时间：
2021-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ereño-Orbea J;Liu X;Sicard T;Kucharska I;Li W;Borovsky D;Cui H;Feng Y;Dimitrov DS;Julien JP
通讯作者：
Julien JP