更新于：2024-11-01

CD8 x DBH

更新于：2024-11-01

基本信息

关联

项与 CD8 x DBH 相关的药物

APL-1401

靶点

CD8 x DBH

作用机制

CD8调节剂 [+1]

在研机构

江苏亚虹医药科技股份有限公司

原研机构

江苏亚虹医药科技股份有限公司

在研适应症

溃疡性结肠炎

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 CD8 x DBH 相关的临床试验

CTR20233635 / Not yet recruiting临床1期

一项在中重度活动期溃疡性结肠炎患者中评价APL-1401的安全性、耐受性、药代动力学和初步疗效的1b期、随机、双盲研究

主要目的： 1. 评价 ALP-1401 在中重度活动期溃疡性结肠炎（UC）患者中的安全性。 2. 考察 APL-1401 在 UC 患者中的药代动力学（PK）特征。次要目的： 1. 收集 APL-1401 在中重度活动期 UC 患者中的初步疗效信号。 2. 探索 APL-1401 在 UC 患者中产生治疗应答的生物标志物。

开始日期-

申办/合作机构

江苏亚虹医药科技股份有限公司

NCT05743010 / Recruiting临床1期

A Phase 1b Randomized, Double-blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis

This is a randomized, double-blind, placebo-controlled, phase 1b study designed to evaluate safety, tolerability, PK, and preliminary efficacy of APL-1401 in patients with moderately to severely active UC. This study comprises 3 periods including screening period (D-28
D-1), treatment period (D1-D28), and safety follow-up period(D29-D58).

开始日期2023-01-26

申办/合作机构

江苏亚虹医药科技股份有限公司

100 项与 CD8 x DBH 相关的临床结果

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100 项与 CD8 x DBH 相关的转化医学

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0 项与 CD8 x DBH 相关的专利（医药）

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项与 CD8 x DBH 相关的文献（医药）

2010-11-01·Journal of Comparative Pathology4区 · 农林科学

Characterization of Autonomic Nerve Markers and Lymphocyte Subsets in the Ileal Peyer’s Patch of Pigs Infected Experimentally with Brachyspira hyodysenteriae

4区 · 农林科学

Article

作者: A. Winnicka ; P. Podlasz ; W. Sienkiewicz ; J. Zmudzki ; W. Wasowicz ; M. Lakomy ; J. Kaleczyc

The aim of the present study was to investigate potential interrelationships between immune and neural elements of Peyer's patches in normal pigs (n=8) and in pigs infected experimentally with Brachyspira hyodysenteriae and suffering from swine dysentery (n=8). Assessment of tissue concentration of neuropeptides by enzyme linked immunosorbent assay revealed increased levels of galanin (GAL) and substance P (SP) in samples from the infected animals. In contrast, concentrations of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were similar in both groups. Immunohistochemistry demonstrated reactivity of nerve fibres with antibodies specific for dopamine β hydroxylase, vesicular acetylcholine transporter, SOM, GAL, VIP and SP in the interfollicular region and peripheral areas of the Peyer's patch lymphoid follicles. In the dysenteric pigs, the GAL-positive nerve fibres were more numerous and more intensely labelled than those in the normal animals. Flow cytometry revealed a decreased percentage of CD21(+) lymphocytes and lymphocytes expressing T-cell receptor (TCR)-γ, with or without CD8 (TCR-γ(+)CD8(-) and TCR-γ(+)CD8(+)), in the dysenteric pigs as compared with the normal animals. Percentages of other lymphocyte subsets (CD2(+), CD4(+), CD5(+), CD8(+), CD5(-)CD8(+)) were comparable between the groups. Immunohistochemical investigations generally correlated with results obtained by flow cytometry related to lymphocyte subpopulations. Swine dysentery can therefore affect neuroimmunomodulatory processes in the ileal Peyer's patch, in addition to the large intestine. GAL and SP may play a specific role in this neuroimmune cross-talk.

2005-07-01·Journal of Biological Chemistry2区 · 生物学

A Structural Basis for CD8+ T Cell-dependent Recognition of Non-homologous Peptide Ligands

2区 · 生物学

Article

作者: Klas Kärre ; Adnane Achour ; Jakob Michaëlsson ; Robert A. Harris ; Tatyana Sandalova ; Gunter Schneider ; Jacob Odeberg

Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (KAVYNFATC/M), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM, has also been identified. We herein report the crystal structure of H-2Db.rDBM and a comparison with the crystal structures of the cross-reactive H-2Db.gp33 and non-cross-reactive H-2Db.gp33 (V3L) escape variant (KALYNFATM, 88% identity to gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented in nearly identical manners by H-2Db, with a striking juxtaposition of the central sections of both peptides from residues p3 to p7. The structural similarity provides H-2Db in complex with either a virus-derived or a dopamine beta-mono-oxygenase-derived peptide with a shared antigenic identity that conserves the positioning of the heavy chain and peptide residues that interact with the T cell receptor (TCR). This stands in contrast to the structure of H-2Db.gp33 (V3L), in which a single conserved mutation, also present in rDBM, induces large movements of both the peptide backbone and the side chains that interact with the TCR. The TCR-interacting surfaces of the H-2Db.rDBM and H-2Db.gp33 major histocompatibility complexes are very similar with regard to shape, topology, and charge distribution, providing a structural basis for CD8 T cell activation by molecular mimicry and potential subsequent development of autoreactivity.

2003-09-01·Histochemistry and Cell Biology3区 · 生物学

Close apposition of dynorphin-positive nerve fibres to lymphocytes in the liver suggests opioidergic neuroimmunomodulation

3区 · 生物学

Article

作者: Winfried L. Neuhuber ; Matthias J. T. Kaiser ; Gisa Tiegs

The liver is innervated by sympathetic efferent, spinal afferent, vagal afferent and probably also vagal efferent fibres. To assess potential functional roles of the various neuronal subsets, data on transmitter systems are of crucial importance. This study was aimed at elucidating a possible opioidergic system in the mouse and rat liver. In particular relationships of opioidergic neurons to immune cells were emphasised. Material from perfusion-fixed mice ( n=29) of different strains (BALB/c, NMRI, C57Bl6, SV 129 inbred) and Wistar rats ( n=7) was cryosectioned at 12-14 microm and incubated for single or double immunofluorescence. Antibodies directed against dynorphin A, met-enkephalin, endomorphin 1 and 2, mu, kappa- and delta-opioid receptors (MOR, KOR, DOR), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), CD4, CD8 and macrophages were used. Binding sites were detected using Cy3-, FITC-, DTAF-, Cy2-, Alexa 555- and Texas red-tagged secondary antibodies. Specimens were analysed using confocal laser scanning microscopy (CLSM). Numerous nerve fibres staining for dynorphin were found in periportal areas of both mouse and rat livers. Neither met-enkephalin nor endomorphin could be detected in axons. No immunopositive neuronal cell bodies or other cellular elements were seen. All dynorphin positive fibres costained for TH while not every TH-positive fibre costained for dynorphin. Thus, most if not all dynorphin-positive nerve fibres may be of sympathetic origin. KOR immunostaining could be localised to round mononuclear cells which often costained for CD4, less frequently for CD8 and rarely for the pan-macrophage marker BM8. Altogether, about 45% of KOR-positive cells were identified as T-lymphocytes. In some instances, close appositions of dynorphin-positive axons to KOR-positive cells were revealed by CLSM. No KOR immunoreactivity was detected in nerve fibres. Hence, sympathetic neurons innervating the liver may interfere with inflammatory processes, in addition to their well-established beta(2)-adrenergic effect, via an opioidergic action on immune cells.