更新于：2024-11-01

CD3 x ITGB6

更新于：2024-11-01

基本信息

关联

项与 CD3 x ITGB6 相关的药物

ITGB6 ProTriTAC

靶点

CD3 x ITGB6

作用机制

CD3刺激剂 [+1]

在研机构

Harpoon Therapeutics, Inc.

原研机构

Harpoon Therapeutics, Inc.

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CD3 x ITGB6 相关的临床结果

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100 项与 CD3 x ITGB6 相关的转化医学

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0 项与 CD3 x ITGB6 相关的专利（医药）

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项与 CD3 x ITGB6 相关的文献（医药）

1994-01-01·International Immunology3区 · 医学

Phenotypic and functional assessment of intraepithelial lymphocytes bearing a ‘forbidden’ αβ TCR

3区 · 医学

Article

作者: Peter B. Ernst ; Kenneth Croitoru ; John Blenenstock

Differences in the surface antigen phenotype, such as the expression CD8 as an alpha alpha homodimer or the lack of Thy-1, on intestinal intraepithelial lymphocytes (IEL) are related, in part, to alternative differentiation pathways. The relationship of IEL lacking the pan-T cell marker CD5 to these IEL, their TCR repertoire and function has not been examined directly. We explored the TCR repertoire and function of the CD5- IEL subset in relation to the expression of the 'autospecific' V beta 6 TCR in MIs-1a mice and to gamma delta TCR. The results indicate that CD5 expression was absent on the majority of TCR gamma delta IEL (96.9%) and on a significant proportion of TCR alpha beta IEL (25.0%). Virtually all IEL in DBA/2 (MIs-1a) mice that expressed the 'autospecific' V beta 6 TCR were CD5-, and this correlated with the expression of CD8 alpha alpha. To assess the functional capacity of this subset of IEL, we examined proliferation and IL-2 production in response to TCR activation. Although CD5- IEL proliferated in response to anti-CD3, IEL bearing TCR V beta 6, in MIs-1a mice, were not responsive to TCR-mediated activation. Similarly, TCR gamma delta IEL were not responsive to stimulation by anti-TCR gamma delta antibodies. The addition of exogenous IL-2, however, reconstituted the proliferative response of both TCR gamma delta IEL and the TCR V beta 6 expressing IEL. We conclude that the lack of CD5 defines a unique subset of intraepithelial T cells expressing either TCR gamma delta or alpha beta that include potentially autoreactive cells that remain anergic in the absence of IL-2.

1991-01-01·International Immunology3区 · 医学

Timing of deletion of autoreactive V _β6+ cells and down-modulation of either CD4 orCD8 on phenotypically distinct CD4+8+ subsets of thymocytes expressingintermediate or high levels of T cell receptor

3区 · 医学

Article

作者: Roland Scollay ; Howard T. Petrie ; Richard L. Boyd ; Gary A. Waanders ; Patrice Hugo

In this paper we describe a differentiation sequence amongst adult murine thymocytes which goes from CD4+8+3lo(low) to CD4+8+3int(intermediate) to CD4+8+3hi(high) and then to mature single positive CD3hi thymocytes. Phenotypic characterization of CD4+8+3int/hi cells for a number of other surface markers is consistent with them being in transition from CD4+8+3lo phenotype to mature phenotype. The same observation was made for sensitivity towards ionomycin-mediated apoptosis. In the thymus of Mls-1a mice, where autoreactive TCR-V beta 6+ cells are negatively selected, deletion of TCR-V beta 6+ cells was first detected in the CD4+8+3int subset, and was complete by the CD4+8+3hi stage, suggesting that up-regulation of the TCR/CD3 complex is required for deletion of Mls-1a autoreactive thymocytes. No sign of apoptosis was detected among any fresh thymocyte subsets suggesting that apoptotic cells are rapidly cleared from the thymus. The CD4+8+3int/CD4+8+3hi cells are therefore populations in transit from the typical cortical thymocytes to the mature T-cells.

1990-05-15·Journal of immunology (Baltimore, Md. : 1950)

Expansion of large granular lymphocytes in IL-2-driven 14-day-old fetal thymocytes in organ culture.

Article

作者: Plum, J ; Tison, B ; Leclercq, G ; De Smedt, M ; Koning, F

These experiments were designed to evaluate the role of cytokines in early T cell development within the thymus. By using a thymic organ culture model, we have studied the influence of high dose of IL-2 (10 to 1000 IU/ml) on the cell populations that are generated during 12 days starting from a thymic rudiment of 14-day-old mouse embryo. The IL-2 treatment resulted in the expansion of Thy-1+/-, CD4-, CD8-, CD3-, Fc gamma RII+, CD5 (Lyt-1)-, HSA-, Pgp- 1+, Mel-14- population. These cells had the morphology of large granular lymphocytes and displayed broad cytotoxic activity. In addition, IL-2-treated organ cultures had a dramatic decrease in CD4+CD8+ thymocytes, a marked reduction in TCR-alpha beta+ thymocytes--even more pronounced in the TCR-V beta 6+ and TCR-V beta 8+ thymocytes--and no significant changes in the number of TCR-gamma delta+ as compared to control organ cultures.

项与 CD3 x ITGB6 相关的新闻（医药）

2023-10-09

·药研网

Seagen押注的癌症潜力靶点：ITGB6

2023年8月，Seagen启动ITGB6 ADC药物SGN-B6A的三期临床，旨在观察SGN-B6A在治疗NSCLC方面是否比多西他赛更有效。该药是公开资料显示的唯一一个进入临床的ITGB6药物，也是Seagen重点产品之一。ITGB6是整合蛋白αvβ6的β6亚基，是控制整个异二聚体αvβ6表达的关键性亚单位。整合素整合素是一种细胞表面跨膜糖蛋白受体，作用是介导细胞与胞外环境的连接。大多数整合素参与细胞-细胞外基质（ECM）相互作用，而其中一些则参与细胞-细胞相互作用。整合素在细胞与其周围环境之间传递双向信号，并参与调节细胞的各种行为，包括细胞增殖、迁移、存活、组织侵袭和先天免疫。整合素是由非共价结合的 α 和 β 亚基组成的异二聚体。哺乳动物细胞有 18 个不同的整合素 α 亚基和 8 个 β 亚基，它们可以不同的方式结合成 24 种不同的受体异二聚体，具有不同的配体识别和组织分布特征。Pairing of integrin subunits[1]整合素αvβ6整合素αvβ6是由αv和β6整合素亚基组成的异二聚体，每个亚基都由一个大的胞外头、一个灵活的腿部、一个跨膜段和一个短的胞质尾组成。The major structural domains of αvβ6 integrin[2]整合素αvβ6的配体是细胞外基质（ECM）蛋白纤连蛋白、玻连蛋白、腱生蛋白和非活性状态的TGF-β（LAP）。β6 亚基的细胞质尾部将受体与细胞骨架和庞大的细胞内信号网络连接起来。值得注意的是，整合素 β6 细胞质尾含有一个 C 端 11 氨基酸延伸，这是其他整合素所没有的。αvβ6整合素的许多独特功能都是由这一延伸部分产生的，这些功能与癌症尤其相关。整合素β6（ITGB6）是αvβ6整合素形成的限速亚基，它只能与αv结合。因此，αvβ6 整合素的表达取决于只在上皮细胞中表达的 β6 整合素基因的转录活性。整合素 αvβ6 仅在上皮细胞上表达，大多数正常健康组织中表达水平较低。但在癌症和纤维化等疾病中经常上调，在所有实体癌中估计有三分之一上调，其表达与疾病进展和较差的预后相关。多项研究表明，肺癌、乳腺癌、结肠癌、胃癌和卵巢癌等许多癌症的严重程度都与αvβ6的表达有关。总之，αvβ6 在发育、组织修复和肿瘤形成过程中发挥调节上皮重塑的作用。ITGB6蛋白表达情况在研进展目前公开资料显示的ITGB6在研靶向药共两款，包括Seagen的ADC药物SGN-B6A和Harpoon Therapeutics的抗体药物。SGN-B6A由IB6抗体、MMAE和mc-vc linker偶联而成。除了NSCLC的三期，目前还在进行一项单药或与Keytruda联用治疗实体瘤的1期临床。早期临床结果显示，在27例NSCLC患者中cORR位33.3%。Harpoon的抗体药物是通过其ProTriTAC技术构建，是抗ITGB6/CD3/白蛋白抗体，在CD3和白蛋白之间加入可以被肿瘤微环境特异性酶切割的linker和掩蔽肽，因此，该抗体仅在肿瘤组织中被酶切后激活，减少脱靶毒性；同时被酶切后激活的CD3/ITGB6不含白蛋白抗体，半衰期缩短，安全性提升。目前该抗体处于临床前阶段。临床前研究显示，ITGB6 ProTriTAC 对多种表达 ITGB6 的实体瘤具有治疗潜力https://www.harpoontx.com/file.cfm/43/docs/2023_aacr_itgb6_ptt_poster_vfinal.pdf细胞系产品查询投稿丨商务合作加入交流群参考：1. https://doi.org/10.3390/cancers120719102. https://doi.org/10.1016/j.biocel.2018.04.0133. https://doi.org/10.3389/fcell.2022.9203034. doi: 10.2174/138945009788680374往期推荐恒瑞医药生物药管线全梳理2023前三季度Biotech裁员汇总石药集团生物药技术平台及管线梳理新模式的兴起 —— 降解抗体偶联药物（DAC）点击下方“药研网”，关注更多精彩内容

抗体药物偶联物临床1期临床2期临床3期临床结果