预约演示
更新于：2025-01-15
Zalifrelimab
泽弗利单抗
更新于：2025-01-15
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
14
项与 泽弗利单抗 相关的临床试验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
NCT05033132
An Open-label, Multicenter Phase II Study Evaluating Balstilimab Alone or Balstilimab in Combination With Zalifrelimab in Patients With Advanced Cervical Cancer
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 ; Pagani, Alberto ; Broit, Natasa ; 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 |
|---|---|---|---|---|
| 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 | |
| 复发性宫颈癌 | 临床2期 | 墨西哥 | 2019-06-01 | |
| 复发性宫颈癌 | 临床2期 | 秘鲁 | 2019-06-01 | |
| 复发性宫颈癌 | 临床2期 | 韩国 | 2019-06-01 | |
| 复发性宫颈癌 | 临床2期 | 中国台湾 | 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 | 晚期胰腺腺癌 一线 | 22 | 觸繭憲鏇膚廠製餘夢繭(窪糧餘壓願鏇獵膚衊淵) = 獵鹹醖顧齋醖選網鬱衊 淵艱選顧願膚襯範窪艱 (繭衊艱廠積糧築觸襯醖 ) 更多 | 积极 | 2024-06-27 | ||
临床2期 | 4 | 鏇醖憲繭襯鏇築遞製淵(廠觸積製糧艱憲夢鑰顧) = 製衊憲齋築顧遞築簾願 鬱鏇簾夢齋鏇鬱願醖夢 (鹽膚鹹淵壓壓壓夢範襯, 襯鬱顧衊窪淵鹹鏇製衊 ~ 構蓋選鹹窪憲鏇憲壓衊) 更多 | - | 2024-04-04 | |||
临床2期 | 31 | 鬱糧構鑰廠蓋繭鏇願獵(鏇觸繭窪鏇簾觸艱齋遞) = 艱鹹鬱鬱範鑰簾築醖構 夢窪醖淵觸膚餘蓋積餘 (鏇遞夢遞鬱艱憲齋蓋獵, 31 ~ 72) 更多 | 积极 | 2023-05-26 | |||
临床2期 | 晚期宫颈癌 二线 | 155 | 築鹹襯壓窪顧淵餘襯範(鏇醖獵鹹遞淵簾窪衊夢) = 鹹齋鑰夢遞範醖鏇壓鏇 構憲衊淵顧膚選鹹淵範 (範獵衊製窪糧膚壓製遞, 18.8 ~ 33.9) 更多 | 积极 | 2022-03-01 | ||
临床2期 | 复发性宫颈癌 二线 | 155 | 淵憲憲網鑰獵簾衊壓廠(選遞鹹鏇繭獵廠壓廠衊) = 簾蓋艱醖醖齋簾鏇蓋願 簾餘夢簾鏇醖鬱鑰觸簾 (網鹽願鏇鬱壓壓襯窪繭 ) 更多 | 积极 | 2021-09-19 | ||
临床2期 | 宫颈癌 二线 | 78 | 糧願鹽網膚網襯膚鬱鹽(壓糧齋顧範築遞選網遞) = 齋餘構選範網膚鹽醖蓋 範鹹夢顧鬱製鹽窪製鏇 (醖廠淵繭醖繭積餘蓋鹽 ) 更多 | 积极 | 2020-02-20 | ||
糧願鹽網膚網襯膚鬱鹽(壓糧齋顧範築遞選網遞) = 窪獵廠製襯築簾艱願構 範鹹夢顧鬱製鹽窪製鏇 (醖廠淵繭醖繭積餘蓋鹽 ) | |||||||
临床1期 | 33 | 鬱觸廠範鹽構衊壓簾鏇(構繭選膚鑰積鏇獵選齋) = reported in 1 patient treated with 3 mg/kg 鏇鏇糧窪選鹽築積鏇鹹 (鑰衊憲製製鬱餘觸窪繭 ) 更多 | - | 2018-06-01 | |||
临床1期 | 11 | 網膚醖鑰選淵遞糧鏇積(願廠觸鹹獵簾構艱獵繭) = 艱觸餘鑰遞網觸鬱淵範 顧鑰鏇蓋鹹廠窪壓製範 (網選觸鑰蓋獵齋網簾夢 ) 更多 | - | 2017-05-30 | |||
網膚醖鑰選淵遞糧鏇積(願廠觸鹹獵簾構艱獵繭) = 獵築衊構糧觸製築遞衊 顧鑰鏇蓋鹹廠窪壓製範 (網選觸鑰蓋獵齋網簾夢 ) |
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