莫纳利珠单抗(Monalizumab) - 药物靶点：NKG2A_在研适应症：局部晚期非小细胞肺癌，不可切除的非小细胞肺癌，转移性头颈部鳞状细胞癌_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

ANTI-NKG2A、IPH-22、IPH-2201

+ [6]

靶点

NKG2A

作用方式

拮抗剂

作用机制

NKG2A拮抗剂(killer cell lectin like receptor C1 antagonists)

治疗领域

肿瘤呼吸系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

局部晚期非小细胞肺癌不可切除的非小细胞肺癌转移性头颈部鳞状细胞癌+ [5]

非在研适应症

食管腺癌宫颈鳞状细胞癌慢性淋巴细胞白血病+ [12]

原研机构

在研机构

+ [1]

非在研机构-

权益机构

MedImmune Pharma BV

Innate Pharma SA

Novo Nordisk A/S

+ [1]

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)临床3期

特殊审评-

登录后查看时间轴

结构/序列

Sequence Code 10109327H

来源: *****

Sequence Code 10109367L

来源: *****

关联

24

项与莫纳利珠单抗相关的临床试验

NCT07146230

/ Not yet recruiting临床2期IIT

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial 2 (SPRINT 2)

This is a randomized trial evaluating the efficacy and safety of sequential dual-agent immunotherapy and risk-adapted radiotherapy for patients with locally advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score of at least 50%. Participants will be randomized between two dual-agent immunotherapy regimens: durvalumab + monalizumab versus durvalumab + oleclumab.

开始日期2026-03-01

申办/合作机构

Montefiore Medical Center

[+1]

NCT06769126

/ Recruiting临床2期IIT

PRISM: PRecIsion in SCLC Via a Multicohort Study: Randomized Phase II Studies Evaluating Maintenance Durvalumab With or Without Biomarker-Directed Therapy for Extensive Stage Small Cell Lung Cancer (ES-SCLC)

This phase II trial tests how well biomarker tests on patients tumor tissue works in selecting personalized treatments for patients with extensive stage small cell lung cancer (ES-SCLC). Biomarker tests look for certain features in cancer cells that may give doctors more information about what is driving cancer and how to treat it. Based on the biomarker test results, study doctors can determine the subtype of ES-SCLC that study treatments can target. This study also tests different types of maintenance treatment for ES-SCLC with drugs durvalumab, saruparib, ceralasertib or monalizumab. Maintenance treatment is given after initial treatment and is given to help keep the cancer under control and prevent it from getting worse. Immunotherapy with monoclonal antibodies, such as durvalumab and monalizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Saruparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for tumor cell growth. Giving biomarker selected personalized maintenance treatment with durvalumab, saruparib, ceralasertib or monalizumab may work better in treating patients with ES-SCLC.

开始日期2025-11-06

申办/合作机构

SWOG

[+1]

NCT06503614

/ Recruiting临床2期IIT

ENHANCE (Elevated NKG2A and HLA-E Amplify NK/CD8 Checkpoint Engagers): A Phase 2 Trial of Durvalumab (MEDI4736) Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer

This is a phase 2 open-label two cohort study of durvalumab plus monalizumab in patients with BCG-unresponsive or BCG-exposed CIS NMIBC. Arm A will enroll 43 participants who have cancer in situ (CIS) with or without high grade papillary urothelial cancer. Arm B will enroll 17 participants who do not have cancer in situ (CIS) but do have high grade papillary urothelial cancer. Eligible patients will be enrolled to receive up to 13 cycles of monthly combination of monalizumab and durvalumab. Both monalizumab and durvalumab will be administered intravenously (IV) every 28 days.

开始日期2025-02-24

申办/合作机构

Hoosier Cancer Research Network

[+3]

100 项与莫纳利珠单抗相关的临床结果

登录后查看更多信息

100 项与莫纳利珠单抗相关的转化医学

登录后查看更多信息

100 项与莫纳利珠单抗相关的专利（医药）

登录后查看更多信息

28

项与莫纳利珠单抗相关的文献（医药）

2026-02-01·CPT-Pharmacometrics & Systems Pharmacology

Stochastic Gates for Covariate Selection in Population Pharmacokinetics Modeling

Article

作者: Dearden, Richard ; Gibbs, Megan ; Zhou, Diansong ; Kekic, Marija ; Tang, Weifeng ; Nowojewski, Andrzej ; Olabode, Damilola ; Wang, Wenjuan ; Stepanov, Oleg ; Traynor, Carlos ; Richardson, Sam

ABSTRACT:

Covariate selection in population pharmacokinetics modeling is essential for understanding interindividual variability in drug response and optimizing dosing. Traditional stepwise covariate modeling is often time‐consuming, compared to the new machine learning alternatives. This study investigates the use of neural networks with stochastic gates for automated covariate selection, aiming to efficiently identify relevant covariates while penalizing excessive covariate inclusion. On various synthetic datasets, the approach demonstrated robustness in detecting important covariates, overcoming challenges such as high correlations, low covariate frequencies, high interindividual variability, and complex covariate dependencies. In real clinical data from a monalizumab study, the method successfully identified covariates that matched those found by experts. However, for tixagevimab/cilgavimab, it identified a superset of covariates, indicating a potential need for further pruning. This machine learning‐based method enhances the covariate preselection process in population pharmacokinetics model development, offering significant time savings and improving efficiency even under challenging scenarios.

2026-01-06·CLINICAL AND EXPERIMENTAL IMMUNOLOGY

CD40L and IL-4 lymph node-associated signals protect B cells from rituximab-induced ADCC via KIR and NKG2A

Article

作者: Blunt, Matthew D ; Sayegh, Souraya ; Graham, Lara V ; Foxall, Russell B ; Cragg, Mark S ; Khakoo, Salim I ; Ashton-Key, Margaret ; Leandro, Maria ; Reddy, Venkat R

Abstract:

Autoreactive B cells that remain in lymphatic tissue after anti-CD20 antibody therapy are considered a major contributing factor to relapse in patients with autoimmune diseases. Natural killer (NK) cells contribute to the depletion of autoreactive B cells by anti-CD20 antibodies via antibody-dependent cellular cytotoxicity (ADCC). However, the impact of germinal centre–associated signals CD40 ligand (CD40L) and interleukin-4 (IL-4) on ADCC was unknown. This study used a combination of flow cytometry, immunohistochemistry, and ex vivo functional assays using peripheral blood mononuclear cells to investigate how CD40L and IL-4 affect NK cell–B cell interactions. CD40L and IL-4 significantly upregulate human leukocyte antigen (HLA)-E and total HLA Class I expression on the surface of B cells from healthy donors, as well as patients with rheumatoid arthritis and systemic lupus erythematosus. The upregulation of HLA-E and total HLA functions to inhibit B-cell depletion by NK cell–mediated ADCC induced by rituximab via NKG2A and killer cell immunoglobulin-like receptors (KIR). Moreover, B cells that have differentiated through the germinal centre have higher expression of HLA-E and total HLA compared with naive B cells and are more resistant to depletion by rituximab. In accordance with this, blockade of NKG2A and inhibitory KIRs by monalizumab and lirilumab, respectively, increased antibody-dependent cellular cytotoxicity against autologous B cells in vitro. Overall, this study identifies a novel mechanism of resistance of B cells to NK cell cytotoxicity and indicates that blockade of the HLA-E:NKG2A and HLA:KIR checkpoint axes could be beneficial for improving B-cell depletion in patients with autoimmune diseases.

2025-08-01·NATURE MEDICINE

Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase 2 NeoCOAST-2 trial

Article

作者: McGrath, Lara ; Insa, Amelia ; Shim, Byoung Yong ; He, Yun ; Cascone, Tina ; Bielska, Agata A ; Egenod, Thomas ; Provencio Pulla, Mariano ; Forde, Patrick M ; Livi, Lorenzo ; Grenga, Italia ; Kim, Dong-Wan ; Garcia Campelo, Maria Rosario ; Guisier, Florian ; Bylicki, Olivier ; Dowson, Adam ; Bennouna, Jaafar ; Corre, Romain ; Spicer, Jonathan ; Liberman, Moishe ; Metro, Giulio ; Bonanno, Laura ; Yohannes, Alula R ; Kumar, Rakesh ; Kar, Gozde

Abstract:

In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA–IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody–drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) rate. In the modified intention-to-treat population (n = 198; Arm 1, n = 74; Arm 2, n = 70; Arm 4, n = 54), pCR rates were 20.3% (15/74; 95% CI, 11.8–31.2), 25.7% (18/70; 95% CI, 16.0–37.6) and 35.2% (19/54; 95% CI, 22.7–49.4), and mPR rates were 41.9% (31/74; 95% CI, 30.5–53.9), 50.0% (35/70; 95% CI, 37.8–62.2) and 63.0% (34/54; 95% CI, 48.7–75.7) in arms 1, 2, and 4, respectively. In the safety population, 69/74 (93.2%), 66/71 (93.0%), and 51/54 (94.4%) patients underwent surgery, respectively. Overall, grade ≥3 treatment-related adverse events occurred in 27/74 (36.5%), 29/71 (40.8%) and 11/54 (20.4%) patients, respectively. In NeoCOAST-2, the first neoadjuvant trial examining an ADC plus chemo-immunotherapy in resectable NSCLC, pCR rates were highest in the datopotamab-deruxtecan-containing arm, warranting further investigation in larger trials of ADCs and checkpoint inhibition in the neoadjuvant setting. ClinicalTrials.gov identifier: NCT05061550.

146

项与莫纳利珠单抗相关的新闻（医药）

2026-03-01

·蒜哥说

第1个NK细胞免疫检查点候选药物及其继承者

背景当T细胞免疫检查点CTLA-4、PD-1大获成功后，药物开发人员将目标转到了先天免疫细胞如自然杀伤细胞和吞噬细胞的免疫检查点，其中第1个NK细胞免疫检查点候选药物为Lirilumab (IPH2101/BMS-986015)，靶向 Killer细胞免疫球蛋白样受体（Killer-cell immunoglobulin-like receptors, KIRs）；NK细胞免疫检查点其它靶点如NKG2、NCR，也有相关候选药物进入临床。IPH2101已在2期临床中折戟并在后续探索中终止研发，但靶向NKG2A的IPH2201已步入3期临床，如果未来一切顺利，其有可能成为第一个NK细胞免疫检查点候选药物，NK细胞免疫检查点候选药物，也将迎来其登场时刻。 NK细胞受体介绍 NK细胞免疫检查点类受体包含CD16、KIRs、NKG2s、NCRs等等。 Nicholas A Maskalenko, Nature Review Drug Discovery,2022 CD16与T细胞接头CD3一样，被药物研发人员用来作为NK细胞接头；同时基于ADCC机制，CD16已在多款上市药物中，应用于临床。 KIRs成员分类为Ig结构域和长短尾，如KIR2DL1（Killer-cell immunoglobulin-like receptors ,2 Ig Domains, Long cytoplasmic tail, 1），2D为2个Ig结构域，L为长尾；KIR3DS1(Killer-cell immunoglobulin-like receptors ,3 Ig Domains, Short cytoplasmic tail, 1)，3D为3个Ig结构域，S为短尾；其中长尾含ITIM，为抑制信号；短尾为活化信号。成员及其配体见表1，其中KIR2DL1-3和KIR2DS2有候选药物进入临床。表1KIRs成员及其配体 Natural Killer Group 2 Family包含NKG2A-H，其中NKG2A和NKG2D有候选药物进入临床，其中NKG2A候选药物为临床3期。表2NKG2s成员及其配体 Natural Killer cell p包含NKp30、44、46、80，其中数字表示其分子量，其也称为Natural Cytotoxicity Receptors。目前有4个成员，其中NKp30、NKp46有候选药物进入临床阶段。表3 NCRs成员及其配体候选药物 KIRs候选药物 KIR靶点候选药物11个，涉及4家企业，终止2个，仅1个候选药物在2期（Lacutamab）外，其他候选药物皆为临床前或1期阶段。抑制靶点主要为KIR3DL1-3，联合靶点涉及LILRB1、LILRB2、B7-H7、TMIGD2和SIRPα；激活靶点主要为KIR2DS2，主要为CAR-T治疗。近期，Innate Pharma计划启动Lacutamab的3期临床试验。 NKG2候选药物 NKG2候选药物主要靶点为NKG2A和NKG2D；NKG2A候选药物13个，涉及11家企业，终止1项；除1项3期临床外，其它皆为临床前及1期。联合靶点涉及CD3、PD-L1、5T3、HLA-E、CD94、TROP2和CD86。步入3期的候选药物IPH2201既往3期临床存在失利，目前与AZ合作3期试验，虽然2期结果积极，但未来仍然是未知。 NKG2D候选药物23个，涉及12家企业，其中终止10个；该靶点候选药物皆为临床前或临床早期阶段，联合靶点涉及CLAN18.2、CD16、HER2、CD33、IL-15Rα，药物类型以CAR-T/NK为主。 NCRs候选药物 NCR候选药物23个,涉及6家企业，终止4个；该靶点候选药物皆为临床前或临床早期阶段，联合靶点涉及CD16、CD123、BCMA、B7-H3、CD38、GPC3、IL-2、ROR1、CD20等，药物类型以多特异性抗体为主。重要企业-INNATE Innate Pharma在NK细胞检查点布局8个候选药物，布局靶点涉及NPk46、NKG2A、KIR2DL1-3、KIR3DL2，其3期2个候选药物，2期2个终止，1期2个，临床前2个，为该领域研发头部企业。总结 NK细胞作为先天免疫系统重要成员，基于Miss-self机制，在抑制和活化信号平衡中，实现对异常细胞的攻击，激活是信号整合的结果。在肿瘤治疗中，与T细胞检查点不同（逆转适应性免疫的“后天性耗竭”），NK细胞检查点旨在解除先天免疫的“先天性抑制”或打破肿瘤建立的“伪自我”信号；NK细胞作为“快速反应和破防部队”，清除屏障，释放抗原，营造炎症环境；T细胞作为特异性强和具有记忆的主力军团，进行深度清除并建立长期免疫监视；二者是高度互补与协同。 NK细胞检查点赛道的兴起，并非追逐“下一个PD-1”的狂热，而是免疫治疗从 “适应性免疫” 向 “先天-适应性免疫”协同，其价值不在于替代T细胞，而在于提供一套全新的攻击逻辑和逃逸机制破解方案，为肿瘤的治疗提供新的武器选择，让患者更为长久获益。

临床2期免疫疗法细胞疗法临床1期临床3期

2026-02-19

·Business Wire

Number of Shares and Voting Rights of Innate Pharma as of February 19, 2026

MARSEILLE, France--(BUSINESS WIRE)--Regulatory News: Pursuant to the article L. 233-8 II of the French “Code de Commerce” and the article 223-16 of the French stock-market authorities (Autorité des Marchés Financiers, or “AMF”) General Regulation, Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) releases its total number of shares outstanding as well as its voting rights as of February 19, 2026: Total number of shares outstanding: 93,743,243 ordinary shares 6,140 Preferred Shares 2016 7,581 Preferred Shares 2017 Total number of theoretical voting rights (1): Total number of exercisable voting rights (2): 94,484,443 94,465,868 (1) The total number of theoretical voting rights (or “gross” voting rights) is used as the basis for calculating the crossing of shareholding thresholds. In accordance with Article 223-11 of the AMF General Regulation, this number is calculated on the basis of all shares to which voting rights are attached, including shares whose voting rights have been suspended. The total number of theoretical voting rights includes voting rights attached to AGAP 2016, i.e. 130 voting rights for the AGAP 2016-1 and 111 voting rights for the AGAP 2016-2. No voting rights attached to AGAP 2017. (2) The total number of exercisable voting rights (or “net” voting rights) is calculated without taking into account the shares held in treasury by the Company, with suspended voting rights. It is released so as to ensure that the market is adequately informed, in accordance with the recommendation made by the AMF on July 17, 2007. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Leveraging its expertise on antibody-engineering and innovative target identification, Innate Pharma is developing innovative and differentiated next-generation antibody therapeutics. Innate Pharma is advancing a portfolio of differentiated potential first and/or best-in-class assets, focused on areas of high unmet medical need, including IPH4502, a differentiated Nectin-4 ADC developed in solid tumors, lacutamab, an anti-KIR3DL2 antibody developed in cutaneous T cell lymphomas and peripheral T cell lymphomas, and monalizumab, an anti-NKG2A antibody developed in collaboration with AstraZeneca in non-small cell lung cancer. Innate Pharma has established collaborations with leading biopharmaceutical companies, including Sanofi and AstraZeneca, as well as renowned academic and research institutions, to advance innovation in immuno-oncology. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at www.innate-pharma.com and follow us on LinkedIn and X. Information about Innate Pharma shares ISIN code Ticker code LEI FR0010331421 Euronext: IPH Nasdaq: IPHA 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors For a discussion of risks and uncertainties, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma’s website (www.innate-pharma.com), and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2024, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public by the Company. References to the Company’s website and the AMF website are included for information only and the content contained therein, or that can be accessed through them, are not incorporated by reference into, and do not constitute a part of, this press release. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

免疫疗法临床研究

2026-01-11

·BioDialectics

癌症免疫检查点新靶点—CD94/NKG2A-HLA-E轴

CD94/NKG2A是自然杀伤（NK）细胞和T细胞亚群表面表达的抑制性受体，其配体为非经典HLA-I分子HLA-E，构成了先天免疫与适应性免疫的重要调控轴。HLA-E的表面表达依赖于抗原加工相关转运体（TAP）介导的经典HLA-I分子信号肽呈递，仅当结合含p2位甲硫氨酸的九肽时才能稳定表达，进而与CD94/NKG2A结合传递抑制信号。这一轴在生理状态下维持免疫平衡，防止自身免疫损伤。而在肿瘤微环境中，肿瘤细胞常高表达HLA-E，通过与NK细胞、CD8⁺T细胞表面的CD94/NKG2A结合，抑制效应细胞活性，实现免疫逃逸。临床研究发现，多种实体瘤中存在CD8⁺NKG2A⁺肿瘤浸润淋巴细胞（TILs）浸润，且HLA-E高表达与患者不良预后相关。此外，IL-12等细胞因子可诱导肿瘤反应性CD8⁺T细胞表达NKG2A，进一步强化这一免疫抑制轴，为靶向该通路提供了明确的临床依据。一：CD94/NKG2A-HLA-E轴的分子特征与表达调控（一）分子结构与结合特性 CD94/NKG2A是由CD94（KLRD1编码）和NKG2A（KLRC1编码）组成的C型凝集素样异二聚体，通过NKG2A胞内结构域的免疫受体酪氨酸抑制基序（ITIM）传递抑制信号，招募SHP-1磷酸酶阻断细胞活化。其配体HLA-E多态性极低，主要有HLA-E01:01和HLA-E01:03两种亚型，均能与CD94/NKG2A结合，结合亲和力受呈递肽序列影响。（二）细胞表达谱与功能分工 NK细胞：CD94/NKG2A在CD56brightNK细胞（早期成熟阶段，以分泌细胞因子为主）中普遍表达，在CD56dimNK细胞（主要效应亚群）中呈异质性表达，可与杀伤细胞免疫球蛋白样受体（KIR）共表达。 T细胞：CD94/NKG2A表达于部分CD8⁺αβT细胞、γδT细胞（主要为Vδ2⁺Vγ9⁺亚群），在肿瘤微环境中可被IL-12、TGF-β等细胞因子诱导上调。功能差异：CD94/NKG2A与PD-1、TIGIT等其他检查点分子可共表达于同一效应细胞，形成叠加抑制效应，削弱抗肿瘤免疫应答。（三）肿瘤微环境中的调控机制肿瘤细胞通过多种方式强化CD94/NKG2A-HLA-E轴介导的免疫逃逸：高表达HLA-E：利用经典HLA-I分子信号肽稳定HLA-E表达，或通过病毒模拟肽（如CMVUL40蛋白衍生肽）非依赖TAP途径呈递，增强与CD94/NKG2A的结合。诱导效应细胞NKG2A表达：肿瘤微环境中的IL-12等细胞因子，可促进NK细胞、CD8⁺T细胞表达NKG2A，提升对HLA-E的敏感性。协同其他免疫抑制通路：CD94/NKG2A与PD-1等检查点协同作用，形成“多重抑制”，导致效应细胞功能耗竭。二：靶向CD94/NKG2A的治疗策略与临床进展（一）抗NKG2A单克隆抗体的临床探索以莫那利珠单抗（monalizumab）为代表的抗NKG2A单克隆抗体，是首个进入临床的CD94/NKG2A抑制剂，其IgG4亚型设计可避免Fc段介导的效应功能，专注于阻断受体-配体相互作用。临床研究显示：在复发/转移性头颈部鳞状细胞癌（HNSCC）中，monalizumab联合西妥昔单抗（抗EGFR抗体）展现出令人鼓舞的客观缓解率，且安全性良好。在非小细胞肺癌（NSCLC）中，与PD-L1抑制剂度伐利尤单抗联合，无论是新辅助治疗（NeoCOAST试验）还是不可切除III期患者（COAST试验），均显著提升病理完全缓解率和临床获益。不过monalizumab联合曲妥珠单抗治疗HER2阳性乳腺癌的II期试验未达预期，可能与晚期患者NK细胞功能耗竭、肿瘤浸润不足相关。目前正探索用于BCG无应答膀胱癌、错配修复缺陷肿瘤等场景，同时在异基因造血干细胞移植后维持治疗中，评估其增强移植物抗肿瘤（GVT）效应的潜力。（二）下一代抗NKG2A药物的开发为提升疗效、优化安全性，新一代抗NKG2A药物不断涌现：S095029通过工程化改造增强NKG2A结合亲和力，在临床前研究中展现出更强的NK细胞、γδT细胞激活能力，目前正开展结直肠癌、胃癌等适应症的I/II期试验。新型抗体XB628是靶向PD-L1和NKG2A的双特异性抗体，可促进PD-L1⁺肿瘤细胞与NK细胞共定位，比单一抑制剂联合更高效诱导NK细胞介导的肿瘤杀伤，已进入早期临床试验。其他候选药物BRY805、HY-0102等通过结构优化提升抗肿瘤活性，初步临床数据显示良好的耐受性和早期活性信号。（三）过继细胞治疗中的靶向改造基因编辑技术为靶向CD94/NKG2A-HLA-E轴提供了新路径： CRISPR-Cas9敲除：在CAR-NK细胞、CAR-T细胞中敲除NKG2A（KLRC1），可显著增强其对HLA-E高表达肿瘤（如多发性骨髓瘤、AML）的杀伤活性，且避免自身免疫风险。开关受体设计：构建CD94/NKG2A/C开关受体，利用NKG2A胞外域识别HLA-E，通过NKG2C胞内域结合DAP-12传递激活信号，使效应细胞主动识别并杀伤HLA-E⁺肿瘤细胞。通用型CAR-T：CT0590/CT0596等BCMA靶向异体CAR-T产品，通过TRAC/B2m/NKG2A三重敲除，既避免移植物抗宿主病（GvHD）和免疫排斥，又增强抗肿瘤功能，早期临床试验在复发/难治多发性骨髓瘤中显示出初步疗效。三：靶向该轴的挑战与优化方向（一）临床应用的关键挑战生物标志物缺乏：目前尚未明确可有效预测疗效的生物标志物，HLA-E表达水平、NKG2A⁺效应细胞浸润比例等潜在指标的检测标准化仍需完善。适应症选择：该轴在不同肿瘤类型中的作用强度存在差异，需精准筛选获益人群，避免在NK细胞严重耗竭或肿瘤浸润不足的晚期患者中盲目应用。联合策略优化：需明确与化疗、靶向治疗、其他免疫检查点抑制剂的最佳组合方式，平衡疗效与毒性。（二）未来优化路径分层治疗：基于肿瘤HLA-E表达、NKG2A⁺效应细胞比例、HLA基因型等特征，筛选优势人群。联合方案创新：探索与TIGIT抑制剂、γδT细胞激动剂等联合，破解多重免疫抑制。技术迭代：开发组织靶向递送系统，减少脱靶效应。优化过继细胞治疗的编辑效率和体内存活时间。总结思考 CD94/NKG2A-HLA-E轴作为连接先天免疫与适应性免疫的关键检查点，其独特优势在于可同时靶向NK细胞和T细胞，覆盖更广泛的效应细胞群体，为PD-1/PD-L1抑制剂耐药患者提供新的治疗选择。目前，靶向该轴的单克隆抗体、双特异性抗体、基因编辑细胞疗法已进入不同临床阶段，在NSCLC、HNSCC、多发性骨髓瘤等适应症中展现出明确的抗肿瘤活性。未来的核心突破点在于：明确疗效预测生物标志物，实现精准分层治疗。优化联合策略，破解肿瘤微环境的多重免疫抑制。推进下一代药物和细胞疗法的临床转化，进一步提升疗效、降低毒性。 TheCD94/NKG2A-HLA-E axis as a target in cancer immunotherapy: a critical perspective. Clin Cancer Res. 2026 Jan 7. doi: 10.1158/1078-0432.CCR-25-0447.

细胞疗法免疫疗法临床研究临床结果

100 项与莫纳利珠单抗相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	莫纳利珠单抗	-	DB12824

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
局部晚期非小细胞肺癌	临床3期	美国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	中国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	日本	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	澳大利亚	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	巴西	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	加拿大	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	哥伦比亚	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	法国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	德国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	意大利	AstraZeneca PLC	2022-02-07

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03801902 (NRG-LU004, CTgov)	临床1期	复发性非小细胞肺癌 \| 不可切除的非小细胞肺癌 \| 局部晚期非小细胞肺癌	26	Accelerated Hypofractionated Radiation Therapy+Durvalumab (Arm I (CLOSED) (Durvalumab and ACRT))	遞憲築襯鬱網鏇鹽獵壓 = 鹽鏇鏇蓋繭構夢餘餘襯構築築衊遞醖願範壓獵 (積糧鑰簾構鏇顧淵窪繭, 願繭衊鹹醖積選範獵遞 ~ 壓衊獵獵艱範衊糧衊餘) 更多	-	2025-06-19
				Magnetic Resonance Imaging of the Brain+Durvalumab (Arm II (CLOSED) (Durvalumab and Standard RT))	遞憲築襯鬱網鏇鹽獵壓 = 鹹構蓋選衊選鹽鏇襯憲構築築衊遞醖願範壓獵 (積糧鑰簾構鏇顧淵窪繭, 襯獵鹽鬱窪窪窪簾網窪 ~ 構構遞夢顧願膚繭範廠) 更多
NCT03822351 (COAST, ASCO2024) 人工标引	临床2期	不可切除的非小细胞肺癌	189	durvalumab	積構製鏇繭簾廠糧遞製(餘壓網鏇艱獵艱夢製選) = 鏇壓觸築製蓋襯觸顧齋廠艱齋觸淵鑰蓋壓憲窪 (膚壓鏇網醖衊淵獵襯顧, 14.3 ~ 35.9) 更多	积极	2024-05-24
				durvalumab+oleclumab	積構製鏇繭簾廠糧遞製(餘壓網鏇艱獵艱夢製選) = 鹽遞餘鑰築鑰積壓積齋廠艱齋觸淵鑰蓋壓憲窪 (膚壓鏇網醖衊淵獵襯顧, 23.1 ~ 48.4) 更多
NCT03794544 (NeoCOAST, AACR2024) 人工标引	临床2期	可切除非小细胞肺癌新辅助	47	durvalumab	夢壓築廠積齋範鹹繭壓(鹽構憲鏇夢鏇夢鑰鹽網) = Percent CD73+ TC and B cell abundance was higher in patients with MPR vs those without MPR in the durva + ole arm, but not in the durva monotherapy or durva + mona arms. Increased CD8 T cell and NK cell abundance was not associated with MPR in any arm. 艱蓋糧醖鬱窪獵艱積廠 (鑰觸淵鏇壓齋觸鬱廠衊 ) 更多	积极	2024-03-22
				durvalumab+oleclumab
NCT04590963 (INTERLINK-1, CTgov)	临床3期	转移性头颈部鳞状细胞癌	370	Cetuximab+Monalizumab (Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2)	夢衊願鑰顧範窪顧構構(鹹憲鬱餘憲鹽廠繭積鬱) = 鹹膚廠艱積網襯選餘鹹膚觸選鏇憲鑰製觸觸糧 (糧鑰製壓獵鏇齋糧餘鬱, 選醖齋構獵遞選獵衊鑰 ~ 糧築鏇憲網範積醖築觸) 更多	-	2023-11-18
				Placebo+Cetuximab (Placebo Q2W + Cetuximab 400 mg/m^2)	夢衊願鑰顧範窪顧構構(鹹憲鬱餘憲鹽廠繭積鬱) = 蓋醖築襯餘憲範糧製願膚觸選鏇憲鑰製觸觸糧 (糧鑰製壓獵鏇齋糧餘鬱, 餘觸觸製鹽餘鑰構觸襯 ~ 憲範範鹹襯願壓簾顧窪) 更多
NCT03088059 (EORTC-HNCG-1559, ESMO2023)	临床2期	头颈部鳞状细胞癌 PD(L)1	66	Durvalumab + Monalizumab	壓鏇鹹築廠壓網廠蓋築(鑰艱蓋簾蓋鑰壓選蓋艱) = 積鏇鬱簾願構顧觸簾範築糧繭顧製壓觸網製願 (膚鬱選鬱鏇構鏇鏇願範 ) 更多	不佳	2023-10-22
				monalizumab (Physician's choice)	壓鏇鹹築廠壓網廠蓋築(鑰艱蓋簾蓋鑰壓選蓋艱) = 蓋蓋構齋憲廠壓選鑰鬱築糧繭顧製壓觸網製願 (膚鬱選鬱鏇構鏇鏇願範 ) 更多
NCT04590963 (INTERLINK-1, Corporate Publications) 人工标引	临床3期	复发性头颈部鳞状细胞癌	600	Cetuximab+Monalizumab	餘獵繭鬱襯積襯觸範憲(願觸簾鹽製艱膚網範鑰) = not reach 構遞鬱衊顧製觸願築憲 (蓋餘鏇糧遞顧齋夢壓衊 )	不佳	2022-08-01
				Cetuximab+Placebo
NCT03794544 (AACR2022) 人工标引	临床2期	非小细胞肺癌新辅助	84	Durvalumab	憲齋築鏇醖製廠鑰鏇網(壓繭窪製夢膚鑰製簾醖) = 餘膚蓋構壓願艱鏇膚觸網簾窪繭醖襯齋膚廠襯 (鏇鹹艱網艱襯願憲襯構, 2.4 ~ 29.2) 更多	积极	2022-06-15
				Durvalumab+Oleclumab	憲齋築鏇醖製廠鑰鏇網(壓繭窪製夢膚鑰製簾醖) = 淵鹽衊糧遞蓋製鑰膚選網簾窪繭醖襯齋膚廠襯 (鏇鹹艱網艱襯願憲襯構, 5.4 ~ 41.9) 更多
NCT03822351 (COAST, Pubmed \| J Urol)	临床2期	非小细胞肺癌 III期巩固	189	Durvalumab	網築製構齋鬱獵構遞築(憲獵製願繭壓蓋鹹鏇獵) = 憲鬱餘築襯衊淵鏇鹽淵衊餘廠鹹鏇築鏇艱鑰壓 (餘鑰鹽構獵積遞簾齋糧, 9.6 ~ 29.2)	积极	2022-04-22
				Durvalumab+Oleclumab	網築製構齋鬱獵構遞築(憲獵製願繭壓蓋鹹鏇獵) = 觸簾鹹夢壓鹹憲餘觸獵衊餘廠鹹鏇築鏇艱鑰壓 (餘鑰鹽構獵積遞簾齋糧, 18.8 ~ 43.2)
NCT02643550 (ESMO_IO 12021 \| ESMO_IO 22021) 人工标引	临床2期	复发性头颈部鳞状细胞癌一线	40	durvalumab+Monalizumab+cetuximab	齋鹹醖壓鬱獵製選鑰膚(鏇蓋簾構蓋範糧淵獵壓) = 積鹹鬱遞築壓壓鹽範艱鹹壓繭齋醖鏇鬱壓築窪 (選構製積鹽選獵蓋糧遞, 20 ~ 48) 更多	积极	2021-12-09
NCT03088059 (UPSTREAM, Pubmed \| Eur J Cancer Care (Engl)) 人工标引	临床2期	头颈部鳞状细胞癌	26	Monalizumab	遞積淵鏇築廠壓壓窪蓋(選鑰鏇廠願製糧網鬱鹹) = 顧獵憲範積獵簾糧鏇艱窪壓艱壓繭窪襯選醖憲 (廠網願構壓鑰顧齋鬱範 ) 更多	不佳	2021-10-09