An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma

The purpose of this study is to determine the initial safety profile and initial antitumor activity of the combination treatments (immune checkpoint inhibitors [nivolumab, ipilimumab] with investigational drugs [TAK-580, TAK-202 (plozalizumab), vedolizumab]) in the 3 arms when administered to participants with advanced melanoma.

开始日期2016-06-22

申办/合作机构

Millennium Pharmaceuticals, Inc.

NCT02388971 / Withdrawn临床2期

A Randomized, Double-Blind Placebo- Controlled Phase 2a Study to Assess the Effect of CCR2 Antagonism by MLN1202 on Atherosclerotic Inflammation in Subjects With Stable Atherosclerotic Cardiovascular Disease Using FDG PET/CT Imaging

The purpose of this study is to evaluate the effect of MLN1202 on arterial inflammation in participants with stable atherosclerotic cardiovascular disease (CVD) who are receiving standard-of-care (SOC) therapy.

开始日期2016-04-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

EUCTR2014-005142-21-AT / Not yet recruiting临床2期

A Multicenter, Randomized, Double Blind, Placebo Controlled, Proof of Concept, Phase 2 Study to Evaluate the Efficacy and Safety of Weekly Subcutaneous MLN1202, in Improving Diabetic Nephropathy Subjects with Macroalbuminuria - MLN1202 75, 105, 150 mg as add-on to ACE/ARB to treat Diabetic Nephropathy

开始日期2015-07-21

申办/合作机构

Takeda Development Centre Europe Ltd.

100 项与 Plozalizumab 相关的临床结果

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100 项与 Plozalizumab 相关的转化医学

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100 项与 Plozalizumab 相关的专利（医药）

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项与 Plozalizumab 相关的文献（医药）

2023-01-01·Bioinformatics and Biology Insights

A Systems Biology Approach for Investigating Significant Biomarkers and Drug Targets Common Among Patients with Gonorrhea, Chlamydia, and Prostate Cancer: A Pilot Study

Article

作者: Islam, Md. Kobirul ; Feroz, Tasmiah ; Shakil, Md. Shahariar Kabir ; Hossain, Md. Monir ; Noman, Abdulla Al

Having a previous history of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia increases the chance of developing prostate cancer, the second most frequent malignant cancer among men. However, the molecular functions that cause the development of prostate cancer in persons with gonorrhea and chlamydia are yet unknown. In this study, we studied RNA-seq gene expression profiles using computational biology methods to find out potential biomarkers that could help us in understanding the patho-biological mechanisms of gonorrhea, chlamydia, and prostate cancer. Using statistical methods on the Gene Expression Omnibus (GEO) data sets, it was found that a total of 22 distinct differentially expressed genes were shared among these 3 diseases of which 14 were up-regulated (PGRMC1, TSC22D1, SH3BGRL, NNT, CTSC, FRMD3, CCR2, FAM210B, VCL, PTGS1, SLFN11, SLC40A1, PROS1, and DSE) and the remaining 8 genes were down-regulated (PRNP, HINT3, MARCKSL1, TMED10, SH3KBP1, ENSA, DERL1, and KMT2B). Investigation on these 22 unique dysregulated genes using Gene Ontology, BioCarta, KEGG, and Reactome revealed multiple altered molecular pathways, including regulation of amyloid precursor protein catabolic process, ferroptosis, effects on gene expression of Homo sapiens PPAR pathway, and innate immune system R-HSA-168249. Four significant hub proteins namely VCL, SH3KBP1, PRNP, and PGRMC1 were revealed by protein-protein interaction network analysis. By analyzing gene-transcription factors and gene-miRNAs interactions, significant transcription factors (POU2F2, POU2F1, GATA6, and HIVEP1) and posttranscriptional regulator microRNAs (hsa-miR-7-5p) were also identified. Three potential therapeutic compounds namely INCB3284, CCX915, and MLN-1202 were found to interact with up-regulated protein C-C chemokine receptor type 2 (CCR2) in protein-drug interaction analysis. The proposed biomarkers and therapeutic potential molecules could be investigated for potential pharmacological targets and activity in the fight against in patients with gonorrhea, chlamydia, and prostate cancer.

2022-12-01·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

Epitope Mapping of an Anti-Mouse CCR2 Monoclonal Antibody (C₂Mab-6) Using Enzyme-Linked Immunosorbent Assay

Article

作者: Kato, Yukinari ; Yoshikawa, Takeo ; Tanaka, Tomohiro ; Tateyama, Nami ; Asano, Teizo ; Suzuki, Hiroyuki ; Okada, Yuki ; Li, Guanjie ; Kaneko, Mika K. ; Kobayashi, Hiyori ; Nanamiya, Ren ; Isoda, Yu

CC chemokine receptor type-2 (CCR2) is a member of the G protein-coupled receptors, and is mainly expressed on cell surface of immune cells. CCR2 binds to its ligand, C-C motif chemokine 2 (also named as monocyte chemoattractant protein-1), which involves in the tumor progression by modulating the tumor microenvironment. Therefore, the monoclonal antibody (mAb) targeting CCR2 could be one of the strategies for cancer treatment. In this study, we investigated the critical epitope of C₂Mab-6, an anti-mouse CCR2 (mCCR2) mAb developed by N-terminal peptides immunization. We first performed enzyme-linked immunosorbent assay (ELISA) using N-terminal peptides of mCCR2 and demonstrated that C₂Mab-6 recognizes 1-19 amino acids of mCCR2. We further performed ELISA using 20 alanine-substituted peptides of mCCR2. C₂Mab-6 lost the reaction to the alanine-substituted peptides of D3A, N4A, M6A, P8A, Q9A, and F10A. These results indicate that the binding epitope of C₂Mab-6 includes Asp3, Asn4, Met6, Pro8, Gln9, and Phe10 of mCCR2.

2022-08-01·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

Development of an Anti-human CCR2 Monoclonal Antibody (C₂Mab-9) by N-Terminal Peptide Immunization

Article

作者: Kaneko, Mika K. ; Saito, Masaki ; Tanaka, Tomohiro ; Suzuki, Hiroyuki ; Kato, Yukinari ; Li, Guanjie ; Asano, Teizo

The CC chemokine receptor type-2 (CCR2) is one of the members of the G protein-coupled receptor superfamily, which are expressed on the cell surface of immune and tumor cells. CCR2 binds to the C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1), which is produced by various cells, including tumor and immune-related cells. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CCR2 has been desired for treatment and diagnosis. In this study, we established a specific antihuman CCR2 (hCCR2) mAb, C₂Mab-9 (mouse IgG₁, kappa), using the synthetic peptide immunization method. Flow cytometric and immunocytochemical results showed that C₂Mab-9 reacted with hCCR2-expressing U937 (human histiocytic lymphoma) and natural killer cells. Furthermore, C₂Mab-9 showed the moderate binding affinity for both cells. Conclusively, C₂Mab-9 can be a useful tool for analyzing hCCR2-related biological responses.

项与 Plozalizumab 相关的新闻（医药）

2024-08-11

·佰傲谷BioValley

错综复杂的趋化因子

趋化因子系统参与调节细胞迁移、粘附、定位和细胞间相互作用，作用于肿瘤细胞和免疫细胞调节二者细胞活动，高度参与肿瘤的发展过程。根据肿瘤发生过程中所处的阶段、免疫细胞的活化状态、效应与调控反应间的平衡以及趋化因子受体在效应靶细胞和调节性靶细胞上的相对表达，趋化因子会表现出促肿瘤和抗肿瘤两种效应，甚至同一趋化因子作用于不同细胞，具有两种截然相反的效应。一、促瘤趋化因子 1. CCL2：通过CCL2-CCR2轴募集肿瘤相关免疫抑制细胞；介导肿瘤与肿瘤相关巨噬细胞（TAM）相互作用，提高肿瘤干细胞特性、转移能力和治疗抵抗。 2. CXCL1/CXCL8：通过CXCL1/CXCL8-CXCR2轴募集肿瘤相关免疫抑制细胞。 3. CXCL12：通过CXCR4-CXCL12轴促进TAM分化为血管周围TAM细胞，提高血管通透性，使肿瘤细胞向血管内浸润；实体瘤增加骨髓基质细胞中CXCL12的表达，导致表达CXCR4的髓样细胞积聚，影响免疫细胞的发育成熟，CXCR4-CXCL12轴参与Treg向骨髓的迁移。 4. CCR4：在肿瘤微环境（TME）中募集调节性T细胞（Treg）。 5. CCR6：促进Treg细胞在TME原位增殖。 6. CCR8：在TME内DC细胞附近募集Treg，并通过抗原识别使Treg具有免疫抑制作用；通过CCR8-CCL1轴增加Foxp3表达维持Treg细胞的免疫抑制能力。 7. CCR4+Th2、CCR6+Th17、CXCR3+Th1、CXCR5+Tfh，以上4类趋化因子受体分别在不同细胞中的表达，与Treg抑制功能有一定相关性。二、抗瘤趋化因子 1. XCL1：通过XCL1-XCR1轴介导cDC1细胞向肿瘤募集，促进cDC1与CD8+T细胞相互作用，促使T细胞扩增和获得效应器功能。 2. CXCL11：其表达与髓源性抑制细胞（MDSCs）的丰度和CD8+T细胞浸润程度成反比。 3. CCR7：介导cDC1和cDC2细胞从肿瘤向TDLN迁移，启动T细胞的效应功能。 4. CCL21：介导T细胞和DC细胞向肿瘤引流淋巴结（TDLN）募集，其表达减少会影响免疫细胞群定位，最终可能导致T细胞活性降低。 5. CX3CR1：CD8+T细胞接收到CX3CR1信号才能发挥抗肿瘤作用。三、双效趋化因子 1. CCR5：CCR5-CCL5轴介导cDC1向肿瘤募集，能同时募集Treg细胞和CD8+T细胞；调控TAM表型和功能，介导肿瘤与TAM相互作用，提高肿瘤肝细胞性、转移能力、治疗抵抗 2. CXCR3：CXCR3-CXCL9/CXCL10轴也能同时募集Treg和CD8+T细胞；使干细胞样TCF-1+细胞向cDC1细胞募集、在TME中重激活和通过接触IL-2获得效应器功能；调控免疫效应细胞在肿瘤附近的定位。四、药物开发一些趋化因子的研究进入了临床阶段，但总体而言疗效不显著。 1. CXCR3-CXCL9/10/11：IFN-γ是该趋化因子轴的主要驱动因素，联用可以增加效应细胞浸润；瘤内注射CXCL9/10/11等配体或者表达配体的溶瘤病毒，增加效应细胞浸润。 3. CXCR4：使用其拮抗剂 AMD3100， BL-8040可以促进肿瘤的T细胞浸润。 4. CCR4-CCL22/17：用于阻断该轴介导的Treg募集的策略，包括阻断抗体、siRNAs和拮抗剂：（1）CCR4抗体：mogamulizumab (KW-0761)是一种人源化、糖工程IgG1κ单克隆抗体，通过ADCC靶向表达CCR4的细胞。临床试验结果显示它可以消除淋巴瘤中Treg的积累。（2）CCR4小分子抑制剂：FLX475和RPT193，FLX475联合派姆单抗治疗晚期或转移性癌症的1/2期临床试验(NCT03674567)最近已经完成，但尚未被报道；此外GSK 的(GSK2239633) 和AstraZeneca的(AZD-1678，AZD-2098) 也是CCR4的小分子抑制剂。 5. CCL2-CCR2：阻断CCL2-CCR2，可以抑制MDSCs的浸润：（1）抗CCR2抗体：MLN1202，治疗骨转移（NCT01015560）。（2）CCR2小分子抑制剂：PF-04136309，联合白蛋白-紫杉醇/吉西他滨治疗中期静态PDA患者的1b期试验显示，外周血中炎症性单核细胞(IM)减少，而没有在骨髓中积累。但与标准化疗相比，CCR2抑制也会导致肺毒性增加。在另一项1b期试验中PF-04136309和叶酸，不同的标准化疗方案（边缘可切除和局部晚期胰腺癌），是安全的，减少单核细胞从骨髓，TAM浸润原发肿瘤，导致高于预期的客观反应率（49%）。（3）CCR2拮抗剂：CCX872 ，用于治疗胰腺癌，总生存率提高（18个月时29%Vs18.6%）。 6. CCR5：CCR5拮抗剂Maraviroc，在体外模型中将巨噬细胞重新极化为免疫活性表型。目前还在招募的临床试验是卒中后认知障碍：NCT04966429 Safety and Efficacy of Maraviroc in Post-stroke Cognitive Impairment Phase2 7. CXCR1/CXCR2-CXCL8：阻断该轴，抑制肿瘤生长：（1）CXCR1/2抑制剂：Reparixin是一种临床级抑制剂，可在体外抑制乳腺癌的生长。（2）CXCR1/2的小分子拮抗剂：包括SCH479833和SCH527123，在乳腺癌、CRC、自发性结肠癌肝转移和黑色素瘤的异种移植模型中具有抗肿瘤活性。（3）CXCL8阻断抗体：ABX-CXCL8，在异种移植模型中抑制黑色素瘤的生长。总体如麻省总医院Andrew D. Luster教授所言，趋化因子和趋化因子受体很难作为治疗靶点进行开发... Even if chemokines and chemokine receptors represent difficult therapeutic targets, they might help todissect cellular components critical for induction and maintenance of pro- and anti-tumorigenic immune cell states. 参考文献 Hanahan, D. et al. Hallmarks of cancer: the next generation. Cell. 2011; 144: 646-674. Hua, Y. et al. Tumors vs. chronic wounds: an immune cell’sperspective. Front. Immunol. 2019; 10: 2178. Villablanca et al, Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7expression on dendritic cells and dampens antitumor responses. Nat. Med. 2010; 16: 98–105. Binnewies, M. et al, Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity. Cell. 2019; 177: 556–571.e16. Griffith, J.W. et al. Chemokines and chemokinereceptors: positioning cells for host defense and immunity. Annu. Rev. 2014; 32: 659-702. Karan Kohli et al，Key chemokines direct migration of immune cells in solid tumors，Cancer Gene Ther . 2022;29(1):10-21. 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

免疫疗法临床申请

2023-04-25

·医药笔记

AACR：ADC创新层出不穷，中国药企扮演重要角色

▎ArmstrongAACR已经落幕，本文梳理ADC领域的报告。Seagen此前以26亿美元引进荣昌生物的HER2 ADC新药纬迪西妥单抗，此次AACR报告了临床前研究数据，与Tucatinib联合有治疗HER2阳性、HER2低表达的乳腺癌、胃癌的潜力。Seagen汇报了整合素β6 ADC新药 B6A的临床前数据，其能诱导免疫激活而杀伤细胞，带来一种额外的杀伤机制。Seagen同时汇报了期ISAC技术平台，抗体偶联TLR7/8激动剂。第一三共汇报了Trop2 ADC的临床前数据，包括与PD-1联用的潜力，以及HER3 ADC等的数据。宜联生物报告了HER3 ADC新药YL202的临床前数据。宜联生物同时介绍了其TMALIN技术平台，采用了高度亲水linker，偶联极度稳定，但在肿瘤组织可以选择性释放毒素。阿斯利康披露了FRα ADC新药AZD5335的临床前数据，对FRα低表达或高表达卵巢癌均体现出治疗潜力。阿斯利康披露了B7-H4 ADC的临床前研究数据。阿斯利康汇报了EGFR/cMET双抗ADC的临床前数据。恒瑞医药汇报了HER2 ADC新药SHR-A1811、Trop2 ADC新药SHR-A1921的早期临床数据和临床前数据。Zymeworks汇报了NaPi2b ADC、FRα ADC、GPC3 ADC的临床前数据。Bioatla报告了Nectin-4 ADC的临床前数据，在其条件激活抗体CAB技术平台上构建。启德医药报告了HER2 ADC、Trop2 ADC新药GQ1010的临床前数据。ADCT Therapeutics汇报了IL13RA2 ADC新药ADCT-211的临床前数据，PSMA ADC新药ADCT-212，采用PBD毒素。武田报告了免疫刺激型ADC技术平台上开发的CCR2 ADC，采用STING激动剂作为payload。Seven and Eight报告了PD-L1 ADC的临床前数据，payload为TLR7/8激动剂。礼新医药汇报了IL-13RA2 ADC新药LM-306的临床前数据。映恩生物汇报了HER2 ADC、HER3 ADC新药的临床前数据以及HER3 ADC的临床方案。百力司康汇报了HER2 ADC新药BB-1701的临床前数据。普方生物汇报了FRα ADC新药PRO1184的临床前数据以及临床方案。百利药业报告了EGFR/HER3 ADC、HER2 ADC、Trop2 ADC的临床前数据。新加坡Hummingbird Bio汇报了HER3 ADC的临床前数据。加科思汇报了CD73 ADC的临床前数据，payload为STING激动剂。百奥赛图报告了多款双抗ADC的临床前数据，包括HER2/Trop2 ADC、EGFR/cMET ADC、HER3/MET ADC、5T4/MET ADC、HER3/MUC1 ADC、Trop2/EGFR ADC、PTK7/Trop2 ADC、EGFR/MUC1 ADC等。Ambrx汇报了CD70 ADC的临床前数据、PSMA ADC的一期临床方案。康源久远汇报了HER2双抗ADC的临床前数据。赛诺菲汇报了CEACAM5 ADC的临床前数据。Mersana汇报HER2 ADC新药XMT-2056的临床前数据。博锐生物汇报了ROR1双表位双抗ADC的临床前数据。Sutro汇报了ROR1 ADC的临床前数据。LCB汇报了新靶点ADC的临床前数据。普众发现、昂阔医药汇报了CDH6 ADC的临床前数据。总结今年AACR中国企业的参与远超以往，以ADC为例，超过70%的ADC报告都来自中国药企，涌现出许多差异化设计和探索，比如宜联生物的肿瘤微环境选择性释放毒素、百奥赛图多款双抗ADC等等。过去一年多时间，国内ADC新药和技术完成多项重要海外授权交易，也表明了中国药企在ADC领域扮演越来越重要的角色。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

抗体药物偶联物AACR会议临床结果临床1期

100 项与 Plozalizumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10972	Plozalizumab	-	DB12520

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
黑色素瘤	临床2期	美国	Millennium Pharmaceuticals, Inc.	2016-06-22
炎症	临床2期	-	Takeda Pharmaceutical Co., Ltd.	2016-04-01
糖尿病肾病	临床2期	-	Takeda Pharmaceutical Co., Ltd.	2015-05-20
动脉粥样硬化	临床2期	-	Millennium Pharmaceuticals, Inc.	2005-08-01
动脉粥样硬化	临床2期	-	Millennium Pharmaceuticals, Inc.	2005-08-01
多发性硬化症	临床2期	-	Millennium Pharmaceuticals, Inc.	2005-05-01

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临床结果

适应症

分期

评价

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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


NCT02723006 (CTgov)	临床1期	黑色素瘤	22	Nivolumab+TAK-580 (Arm 1: TAK-580 + Nivolumab)	壓獵築衊製獵餘願觸鬱(夢觸襯廠餘簾襯窪製觸) = 夢齋鹹蓋艱遞獵襯觸醖製鏇範製鏇襯壓築獵齋 (蓋餘觸淵築糧鏇鹹鑰鏇, 襯顧鹽膚繭鑰遞憲製衊 ~ 壓鑰壓簾夢範夢構艱襯) 更多	-	2021-04-01
NCT02723006 (CTgov)	临床1期	黑色素瘤	22	Nivolumab+TAK-202 (Arm 2: TAK-202 + Nivolumab)	壓獵築衊製獵餘願觸鬱(夢觸襯廠餘簾襯窪製觸) = 壓鑰觸鹽鏇構鹽選鏇醖製鏇範製鏇襯壓築獵齋 (蓋餘觸淵築糧鏇鹹鑰鏇, 鏇築顧製壓繭襯顧衊襯 ~ 遞遞簾窪糧願遞鬱選鹽) 更多	-	2021-04-01
NCT01015560 (S0916, CTgov)	临床2期	实体瘤 \| 骨转移癌	44	MLN1202	顧齋鹽蓋鏇窪繭獵顧遞(醖衊壓獵遞簾淵範鹽繭) = 餘衊網選衊艱蓋鑰齋糧壓積糧齋齋選選夢鏇窪 (獵廠鬱壓衊糧製蓋願膚, 網淵襯顧製廠窪遞憲蓋 ~ 繭遞衊齋繭鬱鑰蓋齋鏇) 更多	-	2014-05-28