预约演示
更新于：2025-01-22
Zalifrelimab
泽弗利单抗
更新于：2025-01-22
概要
基本信息
药物类型 单克隆抗体 |
别名 A human monoclonal antibody targeting cytotoxic T lymphocyte associated protein 4 (ctla4)、Immunoglobulin G1-kappa, anti-(homo sapiens CTLA4 (cytotoxic tlymphocyte-associated protein 4, cd152))、Zalifrelimab (USAN/INN) + [3] |
靶点 |
作用机制 CTLA4调节剂(细胞毒性T淋巴细胞相关抗原4调节剂) |
原研机构 |
非在研机构 |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)终止 |
特殊审评- |
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结构/序列
Sequence Code 12956574L
来源: *****
Sequence Code 12956979H
来源: *****
关联
15
项与 泽弗利单抗 相关的临床试验NCT06782555
A Phase 1/2 Immunotherapy Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab in Patients with Advanced Solid Malignancies
NCT05375903
A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of UGN-301 (Zalifrelimab) Administered Intravesically as Monotherapy and in Combination With Other Agents in Patients With Recurrent NMIBC
NCT04943848
A Phase I Clinical Trial of Neo-antigen Heat Shock Protein Vaccine (rHSC-DIPGVax) in Combination With Checkpoint Blockade for the Treatment of Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma in Childhood
100 项与 泽弗利单抗 相关的临床结果
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100 项与 泽弗利单抗 相关的转化医学
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100 项与 泽弗利单抗 相关的专利（医药）
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84
项与 泽弗利单抗 相关的文献（医药）2024-07-02PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy
Article
作者: Allison, James P. ; Liu, Huey ; Mok, Stephen ; Ağaç Çobanoğlu, Didem ; Mancuso, James J.
Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy.
2024-05-01Skin therapy letter
Long-Term Efficacy of Tildrakizumab in the Treatment of Psoriasis.
Article
作者: Woo, Taylor Evart ; Wytsma, Jennifer ; Parsons, Laurie
The pathogenesis of psoriasis has been linked to autoimmune and autoinflammatory traits that result in atypical cytokine and keratinocyte activation and proliferation. Many cytokine pathways are involved in the development of inflammation with interleukin-23 (IL-23) playing a significant role in plaque-type psoriasis. Biologic agents that target specific cytokines have shown to be effective therapies in the treatment of plaque-type psoriasis over other conventional treatments such as systemic retinoids. Tildrakizumab is an immunoglobulin G1-kappa monoclonal antibody that inhibits the IL-23/IL-17 pathway and has demonstrated through two three-part randomized Phase 3 clinical trials (reSURFACE 1 and reSURFACE 2) and their extension trials to be an efficacious and safe therapy for the targeted treatment of moderate-to-severe plaque-type psoriasis.
2024-04-01Journal for immunotherapy of cancer
Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade
Article
作者: Ogbourne, Steven M ; Shelley, Daniel ; Brooks, Kelly M ; Ferguson, Blake ; Wilson, Emily S ; Stewart, Praphaporn ; Gordon, Victoria A ; Reddell, Paul W ; Appendino, Giovanni ; Hendrawan, Kevin ; McMahon, Tracey ; Broit, Natasa ; Pagani, Alberto ; Johns, Jenny ; Koyama, Motoko ; Cullen, Jason K ; Lim, Yi Chieh ; Yap, Pei-Yi ; Nguyen, Tam Hong ; de Souza, Marjorie M A ; Bruce, Zara C ; Parsons, Peter G ; Boyle, Glen M ; Handoko, Herlina ; Simmons, Jacinta L
Background:
Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.) injection of TT causes vascular disruption with concomitant tumor ablation in several preclinical models of cancer, in addition to various (sub)cutaneous tumors presenting in the veterinary clinic. TT has completed Phase I dose escalation trials, with some patients showing signs of abscopal effects. However, the exact molecular details underpinning its mechanism of action (MoA), together with its immunotherapeutic potential in oncology remain unclear.
Methods:
A combination of microscopy, luciferase assays, immunofluorescence, immunoblotting, subcellular fractionation, intracellular ATP assays, phagocytosis assays and mixed lymphocyte reactions were used to probe the MoA of TT in vitro. In vivo studies with TT used MM649 xenograft, CT-26 and immune checkpoint inhibitor refractory B16-F10-OVA tumor bearing mice, the latter with or without anti-programmed cell death 1 (PD-1)/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb treatment. The effect of TT at injected and non-injected tumors was also assessed.
Results:
Here, we show that TT induces the death of endothelial and cancer cells at therapeutically relevant concentrations via a caspase/gasdermin E-dependent pyroptopic pathway. At therapeutic doses, our data demonstrate that TT acts as a lipotoxin, binding to and promoting mitochondrial/endoplasmic reticulum (ER) dysfunction (leading to unfolded protein responsemt/ERupregulation) with subsequent ATP depletion, organelle swelling, caspase activation, gasdermin E cleavage and induction of terminal necrosis. Consistent with binding to ER membranes, we found that TT treatment promoted activation of the integrated stress response together with the release/externalization of damage-associated molecular patterns (HMGB1, ATP, calreticulin) from cancer cells in vitro and in vivo, characteristics indicative of immunogenic cell death (ICD). Confirmation of ICD in vivo was obtained through vaccination and rechallenge experiments using CT-26 colon carcinoma tumor bearing mice. Furthermore, TT also reduced tumor volume, induced immune cell infiltration, as well as improved survival in B16-F10-OVA tumor bearing mice when combined with immune checkpoint blockade.
Conclusions:
These data demonstrate that TT is an oncolytic small molecule with multiple targets and confirms that cell death induced by this compound has the potential to augment antitumor responses to immunotherapy.
100 项与 泽弗利单抗 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 晚期恶性实体瘤 | 临床2期 | 美国 | 2025-01-08 | |
| 转移性胰腺癌 | 临床2期 | 美国 | 2025-01-08 | |
| 转移性前列腺癌 | 临床2期 | 美国 | 2025-01-08 | |
| 转移性头颈部鳞状细胞癌 | 临床2期 | 美国 | 2025-01-08 | |
| 胰腺癌 | 临床2期 | 西班牙 | - | 2021-09-25 |
| 胰腺导管腺癌 | 临床2期 | 西班牙 | 2021-09-01 | |
| 血管肉瘤 | 临床2期 | - | 2021-02-01 | |
| 转移性软组织肉瘤 | 临床2期 | 美国 | 2020-01-28 | |
| 复发性宫颈癌 | 临床2期 | 美国 | 2019-06-01 | |
| 复发性宫颈癌 | 临床2期 | 巴西 | 2019-06-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 胰腺癌 一线 | 22 | 襯網艱構簾鹹鹽蓋鹽積(鏇壓鬱鬱醖鬱夢膚糧鏇) = 製艱築淵鹽網製顧築構 醖網窪蓋憲鹽製糧選鏇 (襯選鬱衊願憲壓餘顧糧 ) 更多 | 积极 | 2024-06-27 | ||
临床2期 | 4 | 襯膚願壓壓願壓構簾顧(淵憲壓簾願夢繭鏇淵鬱) = 鹹衊蓋遞糧壓醖廠積簾 構壓積構獵膚壓醖衊襯 (繭獵積範鏇獵蓋膚醖蓋, 糧繭積製夢衊顧蓋鹽餘 ~ 夢構鹹夢齋餘製糧選鑰) 更多 | - | 2024-04-04 | |||
临床2期 | 31 | 窪鏇築窪製蓋鬱繭顧選(獵夢鹽壓醖鬱構齋鏇鹹) = 獵網網構繭獵遞襯顧齋 齋鬱壓獵鑰網觸鹹遞鑰 (衊簾顧簾範淵顧範獵範, 31 ~ 72) 更多 | 积极 | 2023-05-26 | |||
临床2期 | 晚期宫颈癌 二线 | 155 | 顧鏇鹽繭艱壓鹹繭獵獵(糧構壓網憲夢構觸鬱衊) = 繭網積選夢鬱壓壓憲遞 鬱窪鑰艱範襯壓醖顧糧 (艱餘顧鬱鬱齋壓製製艱, 18.8 ~ 33.9) 更多 | 积极 | 2022-03-01 | ||
临床2期 | 复发性宫颈癌 二线 | 155 | 壓鑰鬱網獵膚膚鏇網膚(網獵網壓鑰繭餘齋艱積) = 觸積顧獵遞構築選餘網 廠淵淵願廠範淵網選繭 (範餘壓淵醖衊鏇憲築簾 ) 更多 | 积极 | 2021-09-19 | ||
临床2期 | 宫颈癌 二线 | 78 | 糧憲鹹構壓製網鏇齋蓋(顧製糧鹹願構憲觸壓廠) = 壓窪積積鏇製鑰觸壓憲 鏇糧築鏇觸獵選淵齋糧 (築積繭窪製願衊齋窪衊 ) 更多 | 积极 | 2020-02-20 | ||
糧憲鹹構壓製網鏇齋蓋(顧製糧鹹願構憲觸壓廠) = 獵憲醖壓艱醖範遞憲艱 鏇糧築鏇觸獵選淵齋糧 (築積繭窪製願衊齋窪衊 ) | |||||||
临床1期 | 33 | 鏇鹹餘簾壓膚製鹽蓋糧(構鬱觸願膚壓膚鏇糧鹽) = reported in 1 patient treated with 3 mg/kg 鑰築構艱範獵艱構觸構 (觸糧鹹衊積網繭窪選繭 ) 更多 | - | 2018-06-01 | |||
临床1期 | 11 | 觸鑰鏇蓋壓蓋膚衊夢選(鹽醖顧壓衊築繭網顧艱) = 範襯窪醖艱構淵鏇糧鬱 廠壓醖願構淵鹽築壓襯 (鏇窪夢夢獵遞鹹網襯淵 ) 更多 | - | 2017-05-30 | |||
觸鑰鏇蓋壓蓋膚衊夢選(鹽醖顧壓衊築繭網顧艱) = 範範鹽積襯鏇壓構獵積 廠壓醖願構淵鹽築壓襯 (鏇窪夢夢獵遞鹹網襯淵 ) |
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