更新于：2024-04-01

VAMP8

vesicle associated membrane protein 8

更新于：2024-04-01

基本信息

别名

EDB、Endobrevin、VAMP-8

+ [3]

简介

SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (PubMed:23217709, PubMed:25686604). Also required for dense-granule secretion in platelets (PubMed:12130530). Also plays a role in regulated enzyme secretion in pancreatic acinar cells (By similarity). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (PubMed:31694946).

关联

100 项与 VAMP8 相关的临床结果

登录后查看更多信息

100 项与 VAMP8 相关的转化医学

登录后查看更多信息

0 项与 VAMP8 相关的专利（医药）

登录后查看更多信息

473

项与 VAMP8 相关的文献（医药）

2024-04-01·Cell insight

STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy.

Article

作者: Xiaoyu Song ; Yufeng Xi ; Ming Dai ; Tao Li ; Shihao Du ; Yuxin Zhu ; Mengjie Li ; Yunze Li ; Siqi Liu ; Xia Ding ; Xuebiao Yao ; Ying Lai ; Xing Liu

The stimulator of interferon genes (STING) plays a pivotal role in orchestrating innate immunity, and dysregulated activity of STING has been implicated in the pathogenesis of autoimmune diseases. Recent findings suggest that bacterial infection activates STING, relieving ER stress, and triggers non-canonical autophagy by spatially regulating STX17. Despite these insights, the precise mechanism governing the dynamics of autophagosome fusion elicited by STING remains unclear. In this study, we demonstrate that dynamic STING activation guides the autophagy flux, mirroring the trajectory of canonical autophagy adaptors. STING engages in a physical interaction with STX17, and agonist-induced phosphorylation or degradation alleviates STING's inhibitory effects on the assembly of the STX17-SNAP29-VAMP8 complex. Consistent with these findings, degradation-deficient mutants hinder autophagy flux by impeding STX17-mediated autophagosome-lysosome fusion. Moreover, STING mutants associated with lupus disrupt the assembly of the STX17-SNAP29-VAMP8 complex and autophagy process, which lead to persistent STING activation and elevated IFN-β production. Our results highlight that the intracellular trajectory of STING, coupled with autophagy flux, guides the assembly and membrane fusion of the STX17-SNAP29-VAMP8 complex, ensuring the accurate regulation of innate immunity.

2024-02-20·International immunopharmacology

Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration.

Article

作者: Dongxue Wang ; Yutao Wang ; Junfeng Shi ; Wenyi Jiang ; Wenting Huang ; Keyang Chen ; Xue Wang ; Gongchun Zhang ; Yuankuan Li ; Chengkun Cao ; Kwang-Youl Lee ; Li Lin

Poststroke inflammation is essential in the mechanism of secondary injury, and it is orchestrated by resident microglia, astrocytes, and circulating immune cells. Edaravone dexborneol (EDB) is a combination of edaravone and borneol that has been identified as a clinical protectant for stroke management. In this study, we verified the anti-inflammatory effect of EDB in the mouse model of ischemia and investigated its modulatory action on inflammation-related cells. C57BL/6 male mice, which had the transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with EDB (15 mg/kg). EDB administration significantly reduced the brain infarction and improved the sensorimotor function after stroke. And EDB alleviated the neuroinflammation by restraining the polarization of microglia/macrophages and astrocyte toward proinflammatory phenotype and inhibiting the production of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) and chemokines (including MCP-1 and CXCL1). Furthermore, EDB ameliorated the MCAO-induced impairment of Blood-brain barrier (BBB) by suppressing the degradation of tight junction protein and attenuated the accumulation of peripheral leukocytes in the ischemic brain. Additionally, systemic EDB administration inhibited the macrophage phenotypic shift toward the M1 phenotype and the macrophage-dependent inflammatory response in the spleen and blood. Collectively, EDB protects against ischemic stroke injury by inhibiting the proinflammatory activation of microglia/macrophages and astrocytes and through reduction by invasion of circulating immune cells, which reduces central and peripheral inflammation following stroke.

2024-02-09·Cell reports

Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion.

Article

作者: Denghao Zheng ; Mindan Tong ; Shen Zhang ; Yi Pan ; Yanxiang Zhao ; Qing Zhong ; Xiaoxia Liu

Autophagy is crucial for degrading and recycling cellular components. Fusion between autophagosomes and lysosomes is pivotal, directing autophagic cargo to degradation. This process is driven by STX17-SNAP29-VAMP8 and STX7-SNAP29-YKT6 in mammalian cells. However, the interaction between STX17 and YKT6 and its significance remain to be revealed. In this study, we challenge the notion that STX17 and YKT6 function independently in autophagosome-lysosome fusion. YKT6, through its SNARE domain, forms a complex with STX17 and SNAP29 on autophagosomes, enhancing autophagy flux. VAMP8 displaces YKT6 from this complex, leading to the formation of the fusogenic complex STX17-SNAP29-VAMP8. We demonstrated that the YKT6-SNAP29-STX17 complex facilitates both lipid and content mixing driven by STX17-SNAP29-VAMP8, suggesting a priming role of YKT6 for efficient membrane fusion. Our results provide a potential regulation mechanism of autophagosome-lysosome fusion, highlighting the importance of YKT6 and its interactions with STX17 and SNAP29 in promoting autophagy flux.

项与 VAMP8 相关的新闻（医药）

2024-02-04

·生物制品圈

ADC到XDC，抗体偶联药物5大要素，挖掘创新根本源泉

从ADC到XDC，偶联药物未来趋势，将聚焦于新的靶抗原、具有新作用机制的有效载荷、新的抗体和载体形式等方面。靶点适应症选择+最优结构组合，是目前研发重点。抗体偶联药物（Antibody-Drug Conjugate，ADC）是将肿瘤靶向抗体(Tumor Targeted Antibody)和小分子细胞毒性药物(Cytotoxic Drug)利用特定的偶联技术通过连接物(Linker)偶联的一类药物。已有不少文章从各个维度介绍过抗体偶联药物，本篇将再次概述抗体偶联药物的五大基本要素（抗原靶点、抗体、连接子、有效载荷及偶联方式）。作用机制：ADC药物，其抗体高特异性靶向识别肿瘤抗原，静脉注射给药后，药物通过血液循环，分布到肿瘤组织并与肿瘤表面抗原结合。ADC与抗原的复合物通过内吞，将其携带的有效载荷内化到肿瘤细胞中，被转运到溶酶体以高效活性形式被释放，通过DNA损伤或抑制微管合成进而诱导癌细胞凋亡。一、靶点ADC制备起点是靶点选择，药物安全性和有效性主要依赖于靶抗原的选择，及与其相互作用。考虑因素：1，靶抗原是否在肿瘤中高表达，而在正常细胞中无或低表达；2，目标抗原是否在肿瘤细胞的细胞膜表面分布，因而才可以被特异性抗体所识别；3，抗原是否不易脱落，以防止抗体与循环内的抗原结合；4，目标抗原是否具有内化特性。已有超过五十来种抗原，被作为ADC所识别的靶抗原，对于靶抗原位点的选择，科学家们探索不同设计策略。肿瘤细胞/肿瘤微环境的重要靶抗原1、癌症细胞中过度表达的靶抗原（分布癌细胞）：GPNMB,CD70,CD56,Trop-2,FRα,Tissue factor，ENPP3，p-cadherin，mesothelin，STEAP1，CEACAM5，Mucin 1,Nectin 4,SLC44A4,PSMA，LIV1,5T4,SC-16,Guanylyl cyclase C；2、驱动致癌基因（分布肿瘤相关成纤维细胞）HER2,EGFR3、肿瘤血管系统中靶抗原（分布蛋白多糖）EDB,ETB,PSMA VEGFR2，ROBO4，Tissue factor4、基质内靶抗原（分布胶原蛋白）Tenascin C、Collagen IV, Periostin5、血液系统恶性肿瘤中靶抗原（分布血细胞）CD22,CD30,CD33，CD79b,CD19,CD138，CD74，CD37，CD19，CD98临床阶段ADC药物靶点分布目前ADC靶点， HER2 赛道愈发激烈，全球已有 3 款 HER2 ADC 获批上市，全球进入临床阶段的HER2，占比超过20%。TROP-2、EGFR、Claudin18.2等靶点也有多家企业在研中，而中国企业迈入了全球研发前列。此外，全球临床前ADC药物已超过400款，临床前的靶点布局较为分散。TROP2 ，全球有1 款 ADC （戈沙妥珠单抗）获批，国产在研管线众多。Nectin-4 ，全球有 1 款ADC（维恩妥尤单抗）获批上市。CLDN18.2 ADC，全球有十多款进入临床阶段，多数均处于早期临床。2023年ESMO大会呈现的ADC靶点多样化。除了传统靶点外，PTK7、FolRα等新靶点也开始崭露头角。二、抗体（Antibody）抗体是ADC设计重要组成部分，应能够特异性的识别肿瘤细胞的靶抗原，并与靶抗原存在较高亲和力。抗体还应具有免疫原性弱、半衰期长、促进有效内化，血液循环稳定性好的特点。抗体根据其重链恒定区序列可分为IgG、 IgA、IgD、IgE和IgM共五类。目前已批准的ADC基本采用免疫球蛋白G（IgG）抗体，亚型包括IgG1、IgG2、IgG3和IgG4。其中IgG1由于其分子量适中、半衰期长、亲和力高、制备简便，发挥较强的Fc效应子功能等特点，在偶联研发中应用最多的亚型。IgG1在血清中含量最高，可通过与Fc受体的高结合亲和力，诱导抗体依赖性细胞介导的细胞毒性（ADCC）、抗体依赖性吞噬作用（ADCP）和补体依赖性细胞毒性（CDC）等强效应功能。ADC的抗体部分可以采用双特异性抗体或单域抗体等多种形式。双抗可针对同一靶抗原的两个不同表位，也可针对两个不同的靶抗原。ADC也可采用单域抗体偶联杀伤性放射性元素或毒性分子等，以开发新型偶联药物。三、连接子（Linker）连接子是ADC重要组成部分，将抗体与有效载荷连接起来。连接子在血液中的稳定性非常重要，当ADC进入肿瘤细胞或被运输到溶酶体，连接子应迅速分解以释放有效载荷。连接子会影响药物-抗体比值（DAR）、有效载荷释放时间、治疗指数和药代动力学/药效学等。连接子可分为可切割和不可切割两种类型。常见连接子包括：缬氨酸-瓜氨酸（VC）连接子、N-琥珀酰亚胺4-（2-吡啶基二硫基）丁酸酯（SPDB）连接子、腙连接子、4-（N-马来酰亚胺甲基）环己烷-1-羧酸琥珀酰亚胺（SMCC）连接子、马来酰亚胺己酰基（MC）连接子、N-琥珀酰亚胺基-4-（2-吡啶基二硫）戊酸酯（SPP）连接子、硫醚连接子、四肽连接子和碳酸酯连接子等。1、可切割连接子可切割的连接子通过多种机制进行裂解，包括腙键的酸不稳定裂解、二硫键的还原裂解和多肽键的酶解等。可切割连接子并非一定会产生旁观者效应，主要取决于释放载荷的膜穿透性和电荷特性。2、不可切割连接子不可切割连接子的ADC，只有在进入肿瘤细胞的溶酶体被蛋白酶降解后，才会释放有效载荷。不可切割连接子被内吞入溶酶体后，连接子不会被降解，连接的抗体则会被降解为氨基酸，形成氨基酸-连接子-小分子细胞毒复合物。该类型由于“连接子-氨基酸残基”带有电荷，限制了其透膜及扩散，因而通常不会产生旁观者效应。连接子优化，主要是为了增加在血浆中的稳定性以及适配旁观者效应；以及适配不同作用机制的毒素。可裂解连接体成为目前ADC应用的主流趋势，然而由于高毒性载荷对循环稳定性的严格要求，“酶敏感多肽技术”逐渐取代“酸敏感连接子技术”。四、有效载荷ADC有效载荷是其最重要的效应组分，常用的分子包括：微管生成抑制剂、DNA损伤因子和DNA转录抑制剂等。微管生成抑制剂，通过与微管结合阻止微管的聚合，从而阻滞细胞周期，产生细胞毒性，发挥抗肿瘤作用。如：au⁃ ristatin、美登素（Maytansine）及其类似物。DNA损伤因子，通过与DNA的小沟结合并促进DNA链烷基化、断裂或交联。如：Calicheamicin、Duocarmycins、 Anthracyclines、Pyrrolobenzodiazepine dimers。DNA转录抑制剂，如：Quinoline Alkaloid （SN-38）和Amatoxin等。其它新型：凋亡诱导剂，RNA剪接抑制剂，烟酰胺磷酸核糖基转移酶抑制剂等。随着技术发展的不断进步，有效载荷类型的探索越来越多。现有毒素进行改构提高疗效难度较大，主要通过毒素的多样化，实现ADC治疗方案及治疗窗口的拓展。基于拓扑异构酶2抑制剂的蒽环类毒素，以及基于RNApolⅡ抑制剂的阿马毒素（α-Amanitin）具有较好的临床前数据。五、偶联方式（Conjugation）偶联方式包括非定点偶联和定点偶联。非定点偶联法，主要有赖氨酸及半胱氨酸偶联。定点偶联，通过基因工程位点进行特异性偶联，实现更均一的ADC，能在特定位点实现细胞毒素的连接。1、非定点偶联偶联选择性差，产品均一性差。最早利用亲电基团，如马来酰亚胺或者N-羟基琥珀酰亚胺（N-Hydroxy Succinimide，NHS）和暴露赖氨酸的氨基反应。呈现随机性，抗体上携带的药物分子数量不相同，产品异质性大，影响PD/PK等参数。还原二硫键的半胱氨酸非定点偶联，是目前使用较多的偶联方式，Enhertu、Trodelvy、Adcetris均使用此方法。单克隆抗体IgG1含有12个链内二硫键和4个链间二硫键。链内二硫键处于抗体两层反向平行的β折叠结构之间，导致较低的反应性。链间二硫键易被还原剂作用，可还原出8个巯基，进一步与连接着反应基团的毒素分子偶联，形成0、2、4、6、8几种主要的药物偶联形式。2、定点偶联定点偶联是未来 ADC 的研发趋势，定点偶联技术可获得均一性更好的ADC药物，提高ADC药物稳定性，降低脱靶毒性。定点偶联技术主要包括：特异性位点偶联技术、非天然氨基酸偶联技术、聚糖偶联技术以及短肽标签偶联技术等。特异性位点偶联技术，如基因泰克的Thiomab技术，通过基因工程技术在抗体特定位置插入半胱氨酸残基，将半胱氨酸上的巯基与小分子毒物偶联，形成DAR值稳定的高均一性的ADC药物。相比于传统随机偶联得到的ADC药物，该技术ADC药物在血浆中具有低聚集性、高稳定性，以及较强的体内外抗肿瘤活性。基于非天然氨基酸（non-natural Amino Acid, nnAA）的技术，为ADC的制备提供了位点特异性的解决方案。人工合成相比天然氨基酸，特异性和稳定性更好的nnAA，通过正交tRNA合成酶、正交tRNA、独特的密码子系统在蛋白质特定位点引入nnAA。聚糖偶联（GlycoConnect）技术，利用大多数IgG单克隆抗体Fc段中含有天门冬酰胺297残基的糖基化修饰，这是一个很适合的特异性药物偶联位点。抗体通过糖苷内切酶切除N端聚糖，剩下糖胺（GlcNAc），添加N-叠氮乙酰半乳糖胺（N-Azidoacetylga-lactosamine，GalNAz）。短肽标签偶联技术，通过将细胞毒素，偶联到含有4到6个氨基酸残基的特定短肽标签上。在抗体中引入独特的短肽标签，在体内或体外进行酶修饰。允许肽标签中的特定氨基酸功能化，并与药物连接剂耦合。将谷氨酰胺标签（Leu-Leu-Gln-Gly， LLQG）引入到抗体分子中，使标签中的谷氨酰胺被mTG识别，转移含胺药物。在抗体的N端或C端，插入被甲酰基甘氨酸生成酶（Formylglycine-Generating Enzyme，FGE）识别的短肽标签LCx⁃ PxR。抗体与FGE共表达后，短肽标签中的半胱氨酸被细胞内酶氧化为含醛甲酰基甘氨酸，可与氨基功能化试剂偶联。引入的位于抗体不同区域的短肽标签，可能会产生免疫原性。从ADC到XDCADC药物技术，通过对原有药物设计，拓展至XDC万物偶联。目前多肽-药物偶联物，以及抗体-放射性核素偶联物关注度较高，其它多种新型偶联药物也在加速研发中。ADC药物通过拆解优化五大核心要素，筛选高表达的靶抗原，特异性平衡的抗体，代谢稳定的连接子，高抗肿瘤活性的有效载荷，以及DAR值均一的偶联技术，以此打造技术壁垒。随着多种新型偶联药物的快速推进，靶向药物也将迈入新时代。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

抗体药物偶联物

2023-06-20

·生物谷

科学家揭示了PPD是一种靶向CMA抑制剂，是非小细胞肺癌治疗的好策略

自噬是细胞中的一种“自噬”现象，自噬小体包裹错误折叠的蛋白质或受损的细胞器，随后与溶酶体融合形成自溶酶体。被包裹的内容物被自溶酶体降解，以实现细胞内环境的稳定和细胞器的更新。自噬是细胞中的一种“自噬”现象，自噬小体包裹错误折叠的蛋白质或受损的细胞器，随后与溶酶体融合形成自溶酶体。被包裹的内容物被自溶酶体降解，以实现细胞内环境的稳定和细胞器的更新。根据自噬的发生过程，自噬可分为巨型自噬、伴侣介导型自噬和微型自噬。其中，CMA是一种选择性的以Lys-Phe-Glu-Arg-Gln(KFERQ)样五肽基序为靶向的蛋白质降解自噬。KFERQ类基序要么存在于初级氨基酸序列中，要么通过翻译后修饰产生，如磷酸化或乙酰化。胞内伴侣热休克同源蛋白70(HSC70)可以识别含有KFERQ样基序的底物蛋白，随后底物-伴侣复合体通过与溶酶体膜蛋白2A型(LAMP2A)结合转移到溶酶体膜上，并驱动LAMP2A型多聚体形成易位复合体，底物通过该复合体进入溶酶体进行降解。图片来源：https://pubmed.ncbi.nlm.nih.gov/37311689/ 近日，来自中国药科大学的研究者们在Br J Pharmacol杂志上发表了题为“Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer therapy”的文章，该研究揭示了PPD是一种靶向CMA抑制剂，可以阻断HSC70LAMP2A相互作用和LAMP2A同源多聚化。抑制CMA而不增加巨噬细胞自噬的调节补偿是非小细胞肺癌治疗的好策略。伴侣介导的自噬(CMA)是一种选择性的针对蛋白质降解的自噬，在多种恶性肿瘤中保持高活性。抑制HSC70和LAMP2A的结合可以有效地阻断CMA。目前，抑制CMA的最具特异性的方法仍然是下调LAMP2A，目前还没有发现抑制CMA的化学抑制剂。用酪胺信号放大(TSA)双免疫荧光法检测NSCLC组织中CMA的表达水平。根据CMA活性进行高含量筛选，以确定潜在的CMA抑制剂。通过药物亲和反应靶标稳定性-质谱法(DARTS-MS)确定了该抑制剂的靶点，并用蛋白质质谱仪进行了验证。通过对CMA的抑制和激活来阐明CMA抑制剂的分子机制。研究者发现，抑制HSC70和LAMP2A之间的相互作用可以阻断非小细胞肺癌中的CMA，并抑制肿瘤的生长。PPD通过干扰HSC70-LAMP2A相互作用首次被确定为CMA的靶向小分子抑制剂。 PPD的结合位点分别位于HSC70的核苷酸结合区E129和LAMP2A的C末端T278。PPD通过抑制HSC70-LAMP2a-eIF2α信号轴，加速蛋白质合成，诱导ROS积累。此外，PPD还通过阻断STX17-SNAP29-VAMP8信号轴，阻止了CMA抑制引起的巨噬细胞自噬的调节补偿。图片来源：https://pubmed.ncbi.nlm.nih.gov/37311689/ PPD阻断非小细胞肺癌CMA的作用机制综上所述，研究者首次报道PPD是非小细胞肺癌中CMA的靶向抑制剂。更重要的是，本研究为开发CMA抑制剂提供了新的策略。靶向抑制HSC70-LAMP2A相互作用或LAMP2A同源多聚化对非小细胞肺癌的治疗具有很强的疗效。（生物谷 Bioon.com）参考文献 Rui-Fang Dong et al. Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer therapy. Br J Pharmacol. 2023 Jun 13. doi: 10.1111/bph.16165.

2023-05-31

·GlobeNewswire-Health Care

Pyxis Oncology Advances PYX-106 and PYX-201 Clinical Programs

First subject dosed in Phase 1 trial of PYX-106, a fully human immunotherapy antibody candidate Second dose level initiated in Phase 1 trial of PYX-201, an antibody-drug conjugate (ADC) candidate Preliminary data from both trials on track for late-2023/early-2024 timeframe Company to present and host investor meetings at Jefferies Healthcare Conference in NYC on June 7, 2023 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical-stage company focused on developing next-generation therapeutics to target difficult-to-treat cancers, today announced dosing of the first subject in the Phase 1 trial of PYX-106. PYX-106 is a fully human immunotherapy antibody candidate that is designed to block the activity of Siglec-15, an immune suppressor expressed across a broad range of tumors. The Company also announced that the second dose level has been initiated in the ongoing Phase 1 trial of PYX-201, a novel antibody-drug conjugate (ADC) product candidate licensed from Pfizer targeting extradomain-B (EDB) of fibronectin, a non-internalizing antigen that is an integral component of the extracellular matrix in tumors. “We are excited to announce dosing of the first subject in the Phase 1 trial of PYX-106 and we are enthusiastic about the potential PYX-106 may hold for patients, particularly those not well served by currently available immunotherapies,” said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology. “We expect to see preliminary data from each of our ongoing Phase 1 trials of PYX-106 and PYX-201, including biomarker results and potential early signs of clinical activity, in the late-2023 to early-2024 timeframe.” Webcast Presentation at Jefferies Healthcare Conference, June 7, 2023 Pyxis Oncology will present a corporate overview at the Jefferies Healthcare Conference at 4:00 pm ET on June 7, 2023. Lara S. Sullivan, M.D., President and Chief Executive Officer, and Pyxis Oncology management team members will be available during the conference for one-on-one meetings with investors. A live webcast of the presentation can be accessed on the Investors section of the Pyxis Oncology website at ir.pyxisoncology.com. Following the live event, a replay of the webcast will be archived for up to 90 days. About PYX-106-101 PYX-106-101 (NCT05718557) is an open-label, multicenter, Phase 1 dose escalation trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PYX-106 in patients with advanced solid tumors in order to determine the recommended dose(s) for future study. Patients with relapsed or refractory solid tumors known to have significant infiltration of M2 macrophages and expression of Siglec-15, including non-small cell lung cancer, breast cancer, endometrial cancer, thyroid cancer, kidney cancer, cholangiocarcinoma, bladder cancer, colorectal cancer, and head and neck squamous cell carcinoma, are eligible to enroll. About PYX-201-101 PYX-201-101 (NCT05720117) is an open-label, multicenter, Phase 1 dose-escalation trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PYX-201. Patients with relapsed or refractory solid tumors known to have significant expression of EDB of fibronectin, including with relapsed or refractory solid tumors, including non-small cell lung cancer, hormone receptor positive breast cancer, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma, soft tissue sarcoma, hepatocellular carcinoma or kidney cancer are eligible to enroll. About PYX-106 PYX-106 is a fully human immunotherapy antibody candidate in development that blocks the activity of Siglec-15, an emerging immune suppressor expressed across a broad range of tumors. Siglec-15 expression does not overlap with one of the most common targets in immuno-oncology, PD-1, supporting its potential use alone and in combination with current immunotherapies. PYX-106 may benefit patients who do not respond to current standards of care. In preclinical studies, PYX-106 has demonstrated broad immune activation, strong binding affinity, and a 7-day half-life. Cumulatively, these advantages may translate to superior anticancer activity and more flexible dosing regimens. About PYX-201 PYX-201 is a novel antibody-drug conjugate (ADC) product candidate licensed from Pfizer targeting extradomain-B (EDB) of fibronectin, a non-internalizing antigen, that is an integral component of the extracellular matrix in tumors. EDB fibronectin is overexpressed in many solid tumors and minimally expressed in most normal adult tissues. About Pyxis Oncology, Inc. Pyxis Oncology, Inc. is a clinical stage company focused on defeating difficult-to-treat cancers. The company is efficiently building next-generation therapeutics that hold the potential for mono and combination therapies. Pyxis Oncology’s therapeutic candidates are designed to directly kill tumor cells and to address the underlying pathologies created by cancer that enable its uncontrollable proliferation and immune evasion. Pyxis Oncology’s antibody-drug conjugates (ADCs) and immuno-oncology (IO) programs employ novel and emerging strategies to target a broad range of solid tumors resistant to current standards of care. To learn more, visit www.pyxisoncology.com or follow us on Twitter and LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.