作者: Zhang, Miao ; Tang, Aoxing ; Zhu, Yingqi ; Zhang, Zichen ; Hu, Mingxing ; Tang, Jingjie ; Wang, Guijun ; Zhu, Shiqiang ; Bi, Zhuangli ; Fan, Yiming ; Liu, Guangqing ; Du, Qingqing ; Cai, Linying

Felis domesticus allergen 1 (Fel d 1), the primary allergen produced by cats, is a key trigger of various allergic symptoms in humans, such as rhinitis, conjunctivitis, and asthma. In this study, a recombinant Fel d 1 protein composed of chain 2 and chain 1 was successfully produced in E. coli, based on a previously reported fusion construct that closely approximates the native allergen. Two antibodies, 2A7 and 6B1, were selected for further study due to their high specificity and complementary epitope recognition. A dual-antibody sandwich ELISA was established using 2A7 as the capture antibody and HRP-conjugated 6B1 as the detection antibody. The assay showed a detection range of 10-500 ng/mL with a sensitivity of 1 ng/mL. Application to feline saliva and fur samples revealed detectable Fel d 1 levels, and results correlated well with commercial kits. Epitope mapping identified distinct α-helical regions targeted by 2A7 and 6B1, and sequence analysis of their variable regions confirmed diverse V(D)J gene usage. This study provides a valuable antibody pair and a sensitive ELISA method for Fel d 1 quantification, with potential applications in allergen exposure assessment and diagnostic development. SCIENTIFIC SECTION: Immunology, Antibodies, and Diagnostics.

2022-03-08·JCI insight1区 · 医学

A TCR mimic monoclonal antibody reactive with the “public” phospho-neoantigen pIRS2/HLA-A*02:01 complex

1区 · 医学

ArticleOA

作者: Korontsvit, Tatyana ; Balderes, Paul J ; Dao, Tao ; O'Reilly, Richard J ; Pohl, Mary Ann ; Scheinberg, David A ; Molvi, Zaki ; Klatt, Martin G ; Mun, Sung Soo ; Lorenz, Ivo C ; Nyakatura, Elisabeth K ; White, Thomas E ; Khan, Abdul G

Phosphopeptides derived from dysregulated protein phosphorylation in cancer cells can be processed and presented by MHC class I and class II molecules and, therefore, represent an untapped class of tumor-specific antigens that could be used as widely expressed "public" cancer neoantigens (NeoAgs). We generated a TCR mimic (TCRm) mAb, 6B1, specific for a phosphopeptide derived from insulin receptor substrate 2 (pIRS2) presented by HLA-A*02:01. The pIRS2 epitope's presentation by HLA-A*02:01 was confirmed by mass spectrometry. The TCRm 6B1 specifically bound to pIRS2/HLA-A2 complex on tumor cell lines that expressed pIRS2 in the context of HLA-A*02:01. Bispecific mAbs engaging CD3 of T cells were able to kill tumor cell lines in a pIRS2- and HLA-A*02:01-restricted manner. Structure modeling shows a prerequisite for an arginine or lysine at the first position to bind mAb. Therefore, 6B1 could recognize phosphopeptides derived from various phosphorylated proteins with similar amino acid compositions. This raised the possibility that a TCRm specific for the pIRS2/HLA-A2 complex could target a range of phosphopeptides presented by HLA-A*02:01 in various tumor cells. This is the first TCRm mAb to our knowledge targeting a phosphopeptide/MHC class I complex; the potential of this class of agents for clinical applications warrants further investigation.

2021-06-01·Virology3区 · 医学

A human bispecific neutralization antibody against four serotypes of dengue virus

3区 · 医学

Article

作者: Yang, Zhixin ; Chen, Lei ; Wang, Rong ; Lu, Jiansheng ; Yu, Yunzhou

In tropical and subtropical countries, dengue virus (DENV) infections have been increasing; however, we still lack effective therapy. In the present study, we aimed to engineer a bispecific antibody (subsequently named LUZ-8F2-6B1), based on monoclonal antibody 6B1, which has anti DENV-1, 2, and 3 activity, and 8F2, which has anti DENV-4 activity. LUZ-8F2-6B1 displayed potent neutralization activity against four serotypes of DENV by binding to the envelop protein. In vivo, we demonstrated that LUZ-8F2-6B1 could provide protection against infection by four serotypes of DENV in a mouse model. In addition, the deletion of nine amino acids in the Fc region (LUZ-8F2-6B1-9del) completely abolished the antibody-dependent enhancement observed at lower doses of the antibody. Thus, LUZ-8F2-6B1 is a promising, safe, and effective agent for the prophylaxis and treatment of DENV infection.

项与乐地单抗相关的新闻（医药）

2022-06-01

·生物谷

非编码RNA: MicroRNA-10a/b通过靶向转化生长因子-b受体抑制糖尿病肾病肾纤维化

糖尿病肾病(DKD)是糖尿病的一种高发并发症，导致糖尿病患者的发病率和死亡率。超过40%的糖尿病患者进展为DKD，使DKD成为终末期肾病(ESRD)的最常见原因，给患者家庭和社会带来了巨大的经济负担。糖尿病肾病(DKD)是糖尿病的一种高发并发症，导致糖尿病患者的发病率和死亡率。超过40%的糖尿病患者进展为DKD，使DKD成为终末期肾病(ESRD)的最常见原因，给患者家庭和社会带来了巨大的经济负担。然而，DKD的潜在机制尚不完全清楚。临床上，DKD是糖尿病的一种主要微血管并发症，其病理特征包括足细胞丢失、肾小球基底膜增厚和基质扩张，导致肾小球硬化。至于肾小管部分，最近的研究表明糖尿病肾脏的肾小管损害早于肾小球损害，表明肾小管和肾小球细胞都参与了DKD的进展。因此，寻找一种针对DKD患者肾小球和肾小管上皮细胞损伤的新疗法是至关重要的。图片来源：https://doi.org/10.1016/j.omtn.2022.04.002 近日，来自南方医科大学的研究者们在Molecular Therapy: Nucleic Acids杂志上发表了题为“MicroRNA-10a/b inhibit TGF-b/Smad-induced renal fibrosis by targeting TGF-b receptor 1 in diabetic kidney disease”的文章，该研究表明肾脏高表达miR-10a/b可能是治疗DKD纤维化的一种有前景的方法。转化生长因子-β/Smad信号在糖尿病肾病(DKD)纤维化的发生发展中起重要作用。然而，针对转化生长因子-b/Smad信号转导中的关键元件的补救措施尚缺乏。在本研究中，研究者发现转化生长因子-b受体1(TGFBR1)是转化生长因子-b/Smad信号转导的关键蛋白，在糖尿病小鼠和DKD患者的肾脏中表达上调。MicroRNA-10a和-10b(miR-10a/b)通过转录后机制调节TGFBR1的诱导。此外，XRN2，一种外核糖核酸酶，被认为有助于影响miR-10a/b的体外成熟。在链脲佐菌素(STZ)诱导的DKD小鼠中，通过慢病毒原位注射方法阻止肾脏miR10a/b的降低，可减轻胶原沉积和足突消失，而剥夺miR-10a/b则加重肾脏纤维化。在机制上，操纵肾脏miR-10a/b影响TGFBR1蛋白表达、转化生长因子-b/Smad信号的激活以及下游促纤维化基因的表达，包括纤维连接蛋白(FN)和α-平滑肌肌动蛋白(a-SMA)。在一组诊断为DKD的患者中，肾脏miR-10a/b的表达下调，而TGFBR1和纤维化的表达均增强。下调miR-10a/b可加重肾纤维化图片来源：https://doi.org/10.1016/j.omtn.2022.04.002 综上所述，本研究表明miR-10a/b可能通过直接靶向TGFBR1和调节糖尿病的转化生长因子-b/Smad信号通路来调节肾脏纤维化。这些发现为DKD的发病机制提供了新的见解，提示靶向miR-10a/b可能是治疗DKD的一种有效的治疗方法。（生物谷 Bioon.com）参考文献 Jinxiang Li et al. MicroRNA-10a/b inhibit TGF-b/Smad-induced renal fibrosis by targeting TGF-b receptor 1 in diabetic kidney disease. Mol Ther Nucleic Acids. 2022 Apr 7;28:488-499. doi: 10.1016/j.omtn.2022.04.002.

100 项与乐地单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	乐地单抗	-	DB06557

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
瘢痕	临床3期	美国	Cambridge Antibody Technology	-
瘢痕	临床3期	欧洲	Cambridge Antibody Technology	-
瘢痕	临床3期	南非	Cambridge Antibody Technology	-
瘢痕	临床3期	-	Genzyme Corp.	-
白内障	临床2期	-	Genzyme Corp.	-
白内障	临床2期	-	Cambridge Antibody Technology	-
增生性玻璃体视网膜病变	临床2期	英国	Cambridge Antibody Technology	-
增生性玻璃体视网膜病变	临床2期	-	Genzyme Corp.	-

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ARVO2004	临床2期	瘢痕	56	Trabio	網醖簾蓋鑰憲襯齋獵選(遞願積簾鏇獵築構範築) = Events coded to 'Eye Disorders' were the most common, comprising 84% of all events; and of these the most common were in the 'Ocular Infections, Irritations and Inflammations' category with 14% Trabio patients and 25% of the placebo patients reporting one or more events 齋鬱製簾膚遞構製繭願 (憲鏇築鏇鏇簾廠蓋襯繭 )	积极	2004-05-01
				Placebo
CAT-152 (ARVO2003)	N/A	TGFß2	-	CAT-152 (100µg)	糧憲窪淵願齋淵餘夢襯(艱鑰構艱積糧襯憲繭憲) = 襯餘衊憲醖觸獵構簾觸憲構餘蓋憲願蓋憲鬱獵 (蓋簾觸蓋廠壓範製製憲 ) 更多	积极	2003-05-01
				Placebo (phosphate buffered saline)	糧糧醖築範齋選餘糧窪(簾觸網鬱範遞憲餘憲鹹) = 繭鏇製壓遞艱鑰範築範淵鬱膚齋鹹獵膚衊積簾 (鹹鏇淵網壓簾獵醖網構 )
ARVO2002	N/A	瘢痕	-	CAT-152 100µg	餘遞餘艱廠憲製鏇構顧(餘餘壓製窪糧襯築醖醖) = 鹽鏇醖廠膚齋餘夢構積壓獵膚顧憲壓淵顧窪餘 (鑰廠壓廠積觸襯繭淵衊 ) 更多	-	2002-12-01
				Placebo	餘遞餘艱廠憲製鏇構顧(餘餘壓製窪糧襯築醖醖) = 鹽鬱齋繭餘築築鏇蓋膚壓獵膚顧憲壓淵顧窪餘 (鑰廠壓廠積觸襯繭淵衊 ) 更多