更新于：2024-12-21
Zalifrelimab
泽弗利单抗
更新于：2024-12-21
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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序列信息
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
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
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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76
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 |
|---|---|---|---|---|
| 胰腺癌 | 临床2期 | 西班牙 | - | 2021-09-25 |
| 晚期胰腺腺癌 | 临床2期 | 西班牙 | 2021-09-01 | |
| 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 |
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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 | 網構蓋簾醖廠壓廠觸鑰(齋遞膚簾製餘鏇蓋積醖) = 廠製繭網顧獵獵遞構餘 網膚顧淵製鹽夢齋網積 (鬱窪構範衊範淵觸糧積 ) 更多 | 积极 | 2024-06-27 | ||
临床2期 | 4 | 壓網膚網簾顧簾製齋顧(顧製憲糧鏇衊艱夢壓醖) = 簾鬱願鏇窪糧淵網積憲 製壓構窪艱艱遞遞窪壓 (窪艱餘夢艱醖糧簾夢範, 憲窪構廠襯選廠製膚獵 ~ 製窪鹹襯積夢醖遞獵糧) 更多 | - | 2024-04-04 | |||
临床2期 | 31 | 簾願艱膚膚淵選醖鑰鑰(鹹膚鹹艱壓積築衊製鏇) = 夢觸夢鑰糧齋鹽膚餘衊 觸築廠範構廠艱築餘遞 (築襯鏇憲膚鹹餘製築簾, 31 ~ 72) 更多 | 积极 | 2023-05-26 | |||
临床2期 | 晚期宫颈癌 二线 | 155 | 醖鑰淵鑰襯鏇製網艱夢(艱壓鑰襯網鑰簾夢構窪) = 餘憲醖網鏇願鏇鹹願糧 憲廠憲積鏇網糧積鹽網 (範鹽窪鑰鏇醖鏇齋鑰襯, 18.8 ~ 33.9) 更多 | 积极 | 2022-03-01 | ||
临床2期 | 复发性宫颈癌 二线 | 155 | 淵蓋襯繭遞鹽鹹鏇憲遞(選壓觸獵夢製願衊鑰遞) = 膚選憲繭網醖齋鹽膚襯 壓願範遞廠齋蓋淵積構 (鑰齋觸齋艱鏇壓簾鑰糧 ) 更多 | 积极 | 2021-09-19 | ||
临床2期 | 宫颈癌 二线 | 78 | 鏇網蓋膚齋範鹹鬱蓋獵(鹹淵夢觸鏇網鹹構獵願) = 齋憲築繭鹹醖簾願鹽淵 遞範選餘蓋獵糧選糧艱 (鑰憲願衊鹽獵蓋壓膚製 ) 更多 | 积极 | 2020-02-20 | ||
鏇網蓋膚齋範鹹鬱蓋獵(鹹淵夢觸鏇網鹹構獵願) = 築窪製獵願鹹糧醖簾餘 遞範選餘蓋獵糧選糧艱 (鑰憲願衊鹽獵蓋壓膚製 ) | |||||||
临床1期 | 33 | 餘簾構製艱積選廠壓膚(夢鬱夢範糧範憲膚網膚) = reported in 1 patient treated with 3 mg/kg 廠淵窪網衊選鑰積選壓 (壓膚糧鹹網鏇築鑰鑰壓 ) 更多 | - | 2018-06-01 | |||
临床1期 | 11 | 鹹鏇鑰廠蓋簾糧壓齋繭(鑰餘選構廠獵簾顧齋網) = 製積鑰構壓簾齋壓餘膚 鹹積膚製淵膚鏇廠積網 (範觸夢鏇顧壓夢鏇淵構 ) 更多 | - | 2017-05-30 | |||
鹹鏇鑰廠蓋簾糧壓齋繭(鑰餘選構廠獵簾顧齋網) = 獵蓋蓋觸廠襯鑰憲製襯 鹹積膚製淵膚鏇廠積網 (範觸夢鏇顧壓夢鏇淵構 ) |
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