更新于：2024-07-01

Lorukafusp alfa

更新于：2024-07-01

概要

研发状态

概要

基本信息

药物类型

融合蛋白

别名

Anti-ganglioside-GD2-antibody-interleukin-2-fusion-protein、APN 301、APN-301

+ [6]

靶点

GD2 x IL-2R

作用机制

GD2抑制剂(唾液神经节苷脂GD2抑制剂)、IL-2R激动剂(白细胞介素-2受体复合体激动剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病其他疾病+ [2]

在研适应症

黑色素瘤神经母细胞瘤视网膜母细胞瘤

非在研适应症

GD2阳性胶质瘤皮肤黑色素瘤复发性神经母细胞瘤+ [3]

原研机构

Lexigen Pharmaceuticals Corp.

在研机构

APEIRON Biologics AGLexigen Pharmaceuticals Corp.

Merck Sharp & Dohme Corp.

非在研机构

National Cancer Institute

EMD Serono, Inc.

Bristol Myers Squibb Co.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

序列信息

Sequence Code 45370L

来源: *****

Sequence Code 616720214H

来源: *****

关联

项与 Lorukafusp alfa 相关的临床试验

NCT03958383 / Suspended临床1/2期IIT

Phase I/II Intratumoral Administration of Hu14.18-IL2, With Local Radiation, Nivolumab and Ipilimumab in Subjects With Advanced Melanoma

This phase I/II trial is designed to determine the maximum tolerated dose or the maximum administered dose of intratumoral administration of hu14.18-IL2 and to evaluate side effects of intratumoral hu14.18-IL2 when given alone, after radiation therapy, after radiation therapy and in combination with nivolumab, and after radiation therapy and in combination with nivolumab and ipilimumab in patients with melanoma that is advanced (stage IV) or with melanoma that cannot be removed by surgery and is considered surgically incurable. Hu14.18-IL2 is a molecule called a fusion protein that can bind to some tumor cells and cause immune cells to become activated to kill tumor cells. Radiation therapy is a type of cancer treatment that uses beams of high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with immune checkpoint inhibitors, such as nivolumab and ipilimumab, can help the body's immune system attack cancer by releasing the "brakes" on the immune system to allow cancer fighting immune cells to remain activated. This study will evaluate whether giving intratumoral hu14.18-IL2 with radiation therapy, nivolumab and ipilimumab has antitumor activity for participants with advanced melanoma.
After completion of study treatment, participants are followed up at 30 days, every 12 weeks for up to 2 years, and then every 6 months thereafter.

开始日期2020-01-30

申办/合作机构

University of Wisconsin-Madison

[+3]

NCT03209869 / Withdrawn临床1期IIT

Treatment of Relapsed or Refractory Neuroblastoma and Osteosarcoma With Ex-Vivo Expanded and Activated Haploidentical NK Cells and Hu14.18-IL2

Subjects with relapsed or refractory neuroblastoma and osteosarcoma will receive ex-vivo expanded and activated natural killer (NK) cells from a haploidentical donor in conjunction with the immunocytokine, hu14.18-IL2.

开始日期2018-03-12

申办/合作机构

University of Wisconsin-Madison

[+3]

NCT01334515 / Completed临床2期IIT

Feasibility/Phase II Study of hu14.18-IL2 Immunocytokine + GM-CSF and Isotretinoin in Patients With Relapsed or Refractory Neuroblastoma

This phase II trial is studying how well hu14.18-interleukin-2 (IL2) fusion protein works when given together with sargramostim and isotretinoin in treating patients with relapsed or refractory neuroblastoma. Biological therapy, such as hu14.18-IL2 fusion protein, and sargramostim work in different ways to stimulate the immune system and stop tumor cells from growing. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving hu14.18-IL2 fusion protein together with sargramostim and isotretinoin may kill more tumor cells.

开始日期2011-09-01

申办/合作机构

The Children's Oncology Group Foundation, Inc.

[+1]

100 项与 Lorukafusp alfa 相关的临床结果

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100 项与 Lorukafusp alfa 相关的转化医学

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100 项与 Lorukafusp alfa 相关的专利（医药）

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项与 Lorukafusp alfa 相关的文献（医药）

2023-12-01·Cell reports

NK cells propagate T cell immunity following in situ tumor vaccination

Article

作者: Kim, KyungMann ; Jagodinsky, Justin C ; Newton, Michael A ; Berg, Tracy ; Clark, Paul A ; Morris, Zachary S ; Sondel, Paul M ; Rakhmilevich, Alexander L ; Erbe, Amy K ; Zuleger, Cindy L ; Ong, Irene M ; Vera, Jessica M ; Tetreault, Kaitlin ; Jin, Won Jong ; Le, Trang ; Albertini, Mark R

We report an in situ vaccination, adaptable to nearly any type of cancer, that combines radiotherapy targeting one tumor and intratumoral injection of this site with tumor-specific antibody and interleukin-2 (IL-2; 3xTx). In a phase I clinical trial, administration of 3xTx (with an immunocytokine fusion of tumor-specific antibody and IL-2, hu14.18-IL2) to subjects with metastatic melanoma increases peripheral CD8⁺ T cell effector polyfunctionality. This suggests the potential for 3xTx to promote antitumor immunity against metastatic tumors. In poorly immunogenic syngeneic murine melanoma or head and neck carcinoma models, 3xTx stimulates CD8⁺ T cell-mediated antitumor responses at targeted and non-targeted tumors. During 3xTx treatment, natural killer (NK) cells promote CTLA4⁺ regulatory T cell (T_reg) apoptosis in non-targeted tumors. This is dependent on NK cell expression of CD86, which is upregulated downstream of KLRK1. NK cell depletion increases T_reg infiltration, diminishing CD8⁺ T cell-dependent antitumor response. These findings demonstrate that NK cells sustain and propagate CD8⁺ T cell immunity following 3xTx.

2022-09-01·Clinical cancer research : an official journal of the American Association for Cancer Research

Anti-GD2 Antibodies Conjugated to IL15 and IL21 Mediate Potent Antitumor Cytotoxicity against Neuroblastoma

Article

作者: Abbas, Shahroze ; Kelly, Michael C. ; Seibert, Charlie ; Zhang, Xiyuan ; Nguyen, Rosa ; Thiele, Carol J. ; Sun, Ming ; Shern, Jack F.

Abstract:

Purpose::

Half of the patients with high-risk neuroblastoma who receive GD2-targeted mAb do not achieve long-term remissions. Recently, the antibody hu14.18 has been linked to IL2 (hu14.18-IL2) to enhance its efficacy and shown promising preclinical and clinical activity. We developed two new immunocytokines (IC) by linking two other γc cytokines, IL15 and IL21, to hu14.18. The purpose of this study was to compare hu14.18-IL15 and -IL21 with hu14.18-IL2 in their ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) against neuroblastoma.

Experimental Design::

We assessed ADCC of hu14.18-IL15 and -IL2 (human cytokines, cross-reactive to mouse) against GD2low and GD2high neuroblastoma cell lines in vitro. T-cell–deficient mice with orthotopic patient-derived xenografts (PDX) and immunocompetent mice with transplantable orthotopic neuroblastoma were used to test all three ICs, including hu14.18-IL21 (murine IL21, not cross-reactive to human). Mechanistic studies were performed using single-cell RNA-sequencing (scRNA-seq).

Results::

hu14.18-IL15 and hu14.18-IL2 mediated equivalent in vitro ADCC by human NK cells. When combined with chemotherapy, all three ICs similarly controlled the growth of PDXs in nude mice with murine NK effector cells. However, hu14.18-IL15 and -IL21 outperformed hu14.18-IL2 in immunocompetent mice with syngeneic neuroblastoma, inducing complete tumor regressions and extending survival. scRNA-seq data revealed an increase in CD8+ T cells and M1 tumor-associated macrophages and decreased regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment.

Conclusions::

Hu14.18-IL15 and Hu14.18-IL21 exhibit robust preclinical activity, warranting further consideration for clinical testing in patients with GD2-expressing neuroblastoma.

2020-07-01·Journal for immunotherapy of cancer2区 · 医学

In situ vaccination at a peripheral tumor site augments response against melanoma brain metastases

2区 · 医学

ArticleOA

作者: Carlson, Peter M ; Arthur, Ian S ; Lubin, Jonathan A ; Jagodinsky, Justin C ; Kler, Jasdeep ; Guy, Emily I ; Anderson, Bryce R ; Morris, Zachary S ; Clark, Paul A ; Kim, Kyung Mann ; Klar, Kelsey A ; Chakravarty, Ishan ; Heinze, Clinton M ; Kuo, John S ; Jin, Won Jong ; Bates, Amber M ; Le, Trang ; Sriramaneni, Raghava N ; Jaquish, Abigail A

Background:

Immune checkpoint inhibition (ICI) alone is not efficacious for a large number of patients with melanoma brain metastases. We previously established an in situ vaccination (ISV) regimen combining radiation and immunocytokine to enhance response to ICIs. Here, we tested whether ISV inhibits the development of brain metastases in a murine melanoma model.

Methods:

B78 (GD2+) melanoma ‘primary’ tumors were engrafted on the right flank of C57BL/6 mice. After 3–4 weeks, primary tumors were treated with ISV (radiation (12 Gy, day 1), α-GD2 immunocytokine (hu14.18-IL2, days 6–10)) and ICI (α-CTLA-4, days 3, 6, 9). Complete response (CR) was defined as no residual tumor observed at treatment day 90. Mice with CR were tested for immune memory by re-engraftment with B78 in the left flank and then the brain. To test ISV efficacy against metastases, tumors were also engrafted in the left flank and brain of previously untreated mice. Tumors were analyzed by quantitative reverse transcription-PCR, immunohistochemistry, flow cytometry and multiplex cytokine assay.

Results:

ISV+α-CTLA-4 resulted in immune memory and rejection of B78 engraftment in the brain in 11 of 12 mice. When B78 was engrafted in brain prior to treatment, ISV+α-CTLA-4 increased survival compared with ICI alone. ISV+α-CTLA-4 eradicated left flank tumors but did not elicit CR at brain sites when tumor cells were engrafted in brain prior to ISV. ISV+α-CTLA-4 increased CD8+ and CD4+ T cells in flank and brain tumors compared with untreated mice. Among ISV + α-CTLA-4 treated mice, left flank tumors showed increased CD8+ infiltration and CD8+:FOXP3+ ratio compared with brain tumors. Flank and brain tumors showed minimal differences in expression of immune checkpoint receptors/ligands or Mhc-1. Cytokine productions were similar in left flank and brain tumors in untreated mice. Following ISV+α-CTLA-4, production of immune-stimulatory cytokines was greater in left flank compared with brain tumor grafts.

Conclusion:

ISV augmented response to ICIs in murine melanoma at brain and extracranial tumor sites. Although baseline tumor-immune microenvironments were similar at brain and extracranial tumor sites, response to ISV+α-CTLA-4 was divergent with reduced infiltration and activation of immune cells in brain tumors. Additional therapies may be needed for effective antitumor immune response against melanoma brain metastases.

项与 Lorukafusp alfa 相关的新闻（医药）

2024-04-09

·Firstwordpharma

Essential Pharma gains neuroblastoma candidate through Renaissance buy

Essential Pharma announced on Tuesday that it acquired Renaissance Pharma for an undisclosed sum, gaining the latter's immunotherapy candidate, dubbed Hu14.18, which is in Phase II development for the treatment of high-risk neuroblastoma."Our acquisition of Hu14.18, the group's second product for treatment of a rare disease, and the first development-stage asset in our portfolio, is a significant milestone," remarked Essential CEO Emma Johnson. Hu14.18 "has already produced positive data in Phase II clinical trials, demonstrating a significant improvement in survival, and we are now committed to developing this immunotherapy to be able to bring it to market."A Phase II trial incorporating Hu14.18 into first-line therapy and within post-consolidation therapy for patients with high-risk neuroblastoma showed positive patient outcomes with 73.7% three-year event-free survival and 86% overall survival (OS). The trial is approaching the five-year OS readouts.Under the deal, Renaissance CEO Simon Ball will continue to work with Essential on the development of Hu14.18, as will many of the Renaissance team. Essential will work with St Jude Children’s Hospital in accordance with their 2023 exclusive license agreement to drive the development and commercialisation of Hu14.18 across the territories licensed to Renaissance. Essential will be responsible for clinical development of Hu14.18 along with defining the optimal route for regulatory approval and commercial launch of the immunotherapy.

临床2期引进/卖出临床结果免疫疗法并购

2024-04-09

·BioSpace

Essential Pharma acquires Renaissance Pharma Ltd with its clinical stage immunotherapy for the treatment of high-risk neuroblastoma

Essential Pharma acquires Renaissance Pharma Ltd with its clinical stage immunotherapy for the treatment of high-risk neuroblastoma First development-stage asset to be added to the Essential Pharma portfolio and second product within rare disease Egham, UK – 9 April 2024 – Essential Pharma, an international specialty pharma group focused on ensuring that patients have sustainable access to low volume, clinically differentiated, niche pharmaceutical products across key therapeutic areas, announces that it has completed the acquisition of the entire issued share capital of Renaissance Pharma Ltd. Renaissance Pharma is a clinical stage pharmaceutical company focused on the development of life changing therapies in paediatric rare disease, with its lead asset being Hu14.18K322A (Hu14.18) – an immunotherapy currently in Phase II clinical development for the treatment of high-risk neuroblastoma (HRNB). The acquisition adds a second product candidate to Essential Pharma’s rare disease portfolio and underlines the group’s strategy of seeking out clinically differentiated medicines in small patient populations. This will be Essential’s first clinical development-stage asset and is targeted at addressing significant unmet needs in paediatric oncology patients. Simon Ball, CEO and co-founder of Renaissance Pharma, who has significant scientific and commercial expertise within the space, will continue to work with Essential Pharma on Hu14.18’s development, as will many of the Renaissance Pharma team. Neuroblastoma represents 7-10% of all childhood cancers and is the most common extracranial cancer in children and the most common cancer in children under one year of age12. Each year, more than 1500 people are diagnosed in Europe and 800 in the US23. Approximately half of all neuroblastoma patients have high risk (HRNB) disease which has an overall survival of ~50% over five years23. The current standard of care includes multiple cycles of chemotherapy, surgery, radiotherapy, stem cell transplantation and anti-GD2 monoclonal antibody (mAb) treatment2. There remains a significant unmet need in the availability of effective and suitable treatments for HRNB. A Phase II trial incorporating Hu14.18 into first-line therapy and additionally, within post-consolidation therapy for HRNB patients, demonstrated positive patient outcomes with 3-year event-free survival (EFS) of 73.7% and overall survival (OS) of 86.0%. Data from this study was published in the Journal of Clinical Oncology in December 2021 and is approaching five-year OS readouts4. Essential Pharma will work with St Jude Children’s Hospital in accordance with the exclusive license agreement that was signed between St Jude’s and Renaissance in 2023, in order to drive forward the development and commercialisation of Hu14.18 across the territories licensed to Renaissance. Essential Pharma will be responsible for clinical development and defining the optimal route for regulatory approval and eventual commercial launch of Hu14.18. Emma Johnson, CEO of Essential Pharma, commented: “Our acquisition of Hu14.18, the group’s second product for treatment of a rare disease, and the first development-stage asset in our portfolio, is a significant milestone for Essential Pharma, demonstrating our commitment to enabling access to clinically-differentiated medicines. Hu14.18 has enormous potential to help high risk neuroblastoma patients, the majority of whom are young children. It has already produced positive data in Phase II clinical trials, demonstrating a significant improvement in survival, and we are now committed to developing this immunotherapy to be able to bring it to market and to patients as quickly as possible.” Lee Morley, Executive Chairman, Renaissance Pharma Ltd, and Non-Executive Director, Essential Pharma, said: “Essential Pharma is the right partner to take Hu14.18 forward. Having worked alongside Emma at EUSA Pharma, a company specialising in oncology and rare disease, I know that she and the Essential Pharma team have the experience and expertise to bring this important product to market and make it available for children with high-risk neuroblastoma.” About Essential Pharma Essential Pharma is an international specialty pharmaceutical group dedicated to maintaining access to clinically differentiated, niche, branded medicines across multiple therapeutic areas. The group has been an important and valued partner to healthcare providers for over 20 years by giving underserved patient populations access to medicines that otherwise might not be available, and addressing clinical unmet needs. Essential Pharma operates globally in more than 70 countries, supplying a portfolio of products with a focus on the central nervous system (CNS), gastroenterology, ophthalmology, and rare disease. The group’s growth strategy is centred on portfolio optimisation and a targeted M&A approach to acquire commercial and late-clinical stage assets in the four therapeutic areas of focus. It is a trusted partner to multiple pharma companies of all sizes, with a proven history of integrating assets and managing complex technology transfers seamlessly while ensuring continuous and sustainable supply to patients. Essential Pharma is backed by Gyrus Capital, an investment firm dedicated to transformational investments in sectors with long-term sustainable growth, including healthcare. For more information, please visit essentialpharmagroup.com CONTACTS ICR Consilium Tracy Cheung/Chris Welsh/Isabelle Abdou Tel: +44 (0) 20 3709 5700 Email: Essentialpharma@consilium-comms.com 1 DuBois SG, Macy, ME, Henderson TO. High-Risk and Relapsed Neuroblastoma: Toward More Cures and Better Outcomes. American Society of Clinical Oncology Educational Book [Internet]. 2022 Jul;(42):768–80. Available from: 2 St. Jude Children’s Hospital. Neuroblastoma. Available from: 3 News Medical Life Sciences. European scientists target high-risk childhood cancer with liquid biopsy. Available from: 4 Furman WL, McCarville B, Shulkin BL, Davidoff A, Krasin M, Hsu CW, et al. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. Journal of Clinical Oncology [Internet]. 2022 Feb 1;40(4):335–44. Available from:

临床结果临床2期免疫疗法引进/卖出并购

2024-04-07

·佰傲谷BioValley

IL-2/IL-2R研究简史

1976年发现的IL-2，在整个免疫治疗史上，有着不可替代的位置。Rosenberg称之为第一个人类肿瘤有效的免疫治疗方法。IL-2/IL-2R受体里程碑研究 1976年 NCI肿瘤细胞生物学实验室的RobertGallo，使用PHA刺激淋巴细胞产生条件培养基培养骨髓细胞，其中90%的T细胞长达9个月的生存维持。在此之前，原代T细胞无法体外培养，是免疫学发展的巨大瓶颈性技术问题。这个未被纯化的成分称之为T细胞生长因子（TCGF）。条件培养基培养骨髓细胞（文献1）1980年NCI肿瘤细胞生物学实验室的RobertGallo，通过离子交换色谱和凝胶分离，从条件培养基中分离浓缩了TCGF，并且得出了大致的分子量约15KD。纯化IL-2电泳（文献2）1983年日本癌症研究基金会肿瘤研究中心，Junji Hamuro等人，克隆了IL-2的基因，完成了测序工作。人们可以完整的了解这个T细胞生长因子的基因和氨基酸序列等基础信息。但是为什么第一个被克隆的细胞因子成为IL-2而不是IL-1呢？原因是，当初有科学家认为，有另外一个细胞因子刺激了IL-2的产生，那个未知的因子应该是1。IL-2序列（文献3）IL-2受体的发现和克隆 1984年Nature发表了三篇IL-2受体α克隆的文章（文献4，5，6），分别来自于Immunex 公司（2002年Amgen收购），NCI，和日本京都大学。 1986年NIH国立儿童健康与人类发育研究所在Science发表文章（文献7），发现了IL-2另外一个受体p70，1986和1987年还有多篇文章报道IL-2 p70受体。1990年日本东北大学医学院，1991京都大学分别发表文章发现IL-2Rγ（文献8，9）。至此，IL-2受体α，β，γ被发现。之后IL-2和受体的结合，被Stanford的科学家解析。IL-2-IL-2Rα，β，γ复合物结构（文献10）IL-2/IL-2R药物开发重组IL-21983年IL-2基因被克隆，是IL-2药物开发的里程碑式基础研究，1983年和1984年多个实验室进行了IL-2的大肠杆菌表达。 IL-2临床试验统计（文献16）1984年11月，一个33岁黑色素瘤转移的病人接受重组IL-2治疗，肿瘤消退，此后病人无疾病生存29年。1985年Rosenberg在肝癌转移小鼠模型注射重组IL-2，获得很好的治疗效果（文献11）。1985年Rosenberg等在新英格兰医学杂志报道，使用IL-2和LAK细胞进行了25个癌症转移病人的临床研究。Rosenberg 2014年发文评述IL-2是第一个人类肿瘤有效的免疫治疗方法（文献13）。 1991年诺华与linigen联合研发的重组IL-2药物 Proleukin（Aldesleukin，阿地白介素）被FDA批准治疗转移性肾癌，1998年批准治疗转移性黑色素瘤。但是因为半衰期短，治疗窗口窄，毒副作用大，且同时刺激Treg活化，限制了临床使用。新型IL-2开发（PEG化，偏向性IL-2） IL-2R有α（CD25），β（CD122），γ（CD132），其中，α为低亲和力受体，且下游无信号传导，β和γ组成中等亲和力的受体，下游可以通过JAK传导信号，在α参与的情况下，亲和力增强为高亲和力受体。IL-2受体（文献17）从1990s开始，很多的科研单位和企业开始，通过突变改变IL-2和不同受体亚单位亲和力，以增加活力，降低毒性。2000年Bayer 设计了BAY50-4798，选择性结合IL-2Raβγ，减少和IL-2βγ的结合，减少IL-2Rβγ+ NK细胞介导的毒性。但是最终临床治疗和传统IL-2比较，没有改善。BAY50-4798结构及作用（文献14）NKTR-214NKTR-214是由美国Nektar公司开发的一种针对CD122 (IL-2Rβ)抗原的偏向型激动剂,其通过靶向作用于CD8+效应T细胞以刺激肿瘤杀伤T细胞的增殖,从而利用患者自身免疫系统对抗癌症。NKTR-214通过对首个肿瘤免疫药物aldesleukin进行聚乙二醇(PEG)修饰,有效克服了其严重的毒副作用并延长起效时间。THOR-707Synthorx公司（赛诺菲25亿美金收购）产品，通过向宿主细胞转入非天然氨基酸，在该位点实现定点PEG偶联，和IL-2Rα低亲和力，但是和IL-2Rβγ有接近天然的亲和力，选择性激活CD8+T细胞，不激活Treg。NCT04009681，A Study Evaluating Safety and TherapeuticActivity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors(THOR-707-101)，Phase1/2SHR-1916 12月25日恒瑞偏向性IL-2，SHR-1916获批临床。SHR-1916是恒瑞医药自主研发的全新PEG修饰和位点突变的IL-2分子，可以通过激活JAK1/JAK3/STAT5信号通路，促进CD8⁺T和NK细胞增殖，发挥抗肿瘤作用。Immunocytokine（抗体-IL2偶联）通过靶向肿瘤抗原抗体将IL-2携带至肿瘤局部，是另外一种策略，可以增加半衰期，增强靶向性，降低毒性。hu14.18-IL2hu14.18-IL2（EMD273063），由EMD Serono研发，是一种抗GD2免疫因子，由抗GD2抗体14.18（抗体）和两分子的IL-2（免疫因子）融合而成的蛋白，主要用于治疗黑色素瘤。临床研究：NCT00590824，Pilothu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma，phase2 在一些高复发风险的黑色素瘤患者中，使用IC治疗的患者出现了长时间的无瘤生存。 L19-IL2Philogen S.p.A.公司研发，L19靶向细胞外基质（ECM）纤维连接蛋白异构体B-FN的的结构域B（ED-B）。NCT02957019，A PhaseI/II Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokineFusion Protein in Combination With Rituximab in Relapsed or Refractory DiffuseLarge B-cell Lymphoma (DLBCL)NCT04362722，IntratumoralAdministration of Daromun in Non-melanoma Skin Cancer Patients (DUNCAN)，phase2Philogen S.p.A.还开发了F16IL2，有多个临床在开展，但是进度未更新。RO6874281RO6874281，来自于Roche，是IL-2突变体与靶向FAP的单抗融合而成的双特异性蛋白，其中靶向肿瘤胶质抗原FAP的单抗用于将蛋白相对准确地定位到肿瘤部位，IL-2突变体部分则偏向性地结合和调控肿瘤微环境中的T细胞表面的IL-2Rβγ二聚体，从而激活微环境中的抗肿瘤免疫效果。 NCT03875079（Metastatic Melanoma），NCT03063762（Metastatic Renal Cell Carcinoma），NCT02627274（联用Trastuzumab or Cetuximab），NCT03386721（实体瘤，联用Atezolizumab），NCT03193190（PDAC）IL-2R抗体阻断性抗体用于炎症性疾病，非阻断性抗体用于肿瘤免疫治疗。阻断性抗体Zinbryta(daclizumab)AbbVie，Inc.和Biogen适用为有多发性硬化症(MS)的复发型成年患者的治疗白介素-2受体阻断抗体7例严重不良反应，主要为脑炎和脑膜炎，这才紧急启动撤市程序。 IL-2R alpha嵌合体抗体Basiliximab/巴利昔单抗/舒莱Novartis预防首次肾移植术后的急性器官排斥国内注册号：S20171040非阻断性抗体RG6292非阻断性CD25抗体，选择性清除Treg。详细内容可阅读：Roche 新型CD25抗体选择性清除调节性T细胞，增强抗肿瘤免疫参考文献Morgan DA, Ruscetti FW, GalloRC: Selective in vitro growth of T lymphocytes from normal human bone marrows.Science 1976, 193: 1007e1008J.W. Mier, R.C. Gallo,Purification and some characteristics of human T-cell growth factor fromphytohemagglutinin-stimulated lymphocyte-conditioned media, Proc.Natl. Acad.Sci. USA (1980)aniguchi T,et al: Structure andexpression of a cloned cDNA for human interleukin-2. Nature 1983, 302:305e310Cosman, D.et al, (1984).Cloning, sequence and expression of human interleukin-2 receptor. Nature 312,768–771.Leonard, W.J.,etal.(1984).Molecular cloning and expression of cDNAs for the human interleukin-2 receptor.Nature 311, 626–631.Nikaido, T., et al (1984).Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311,631–635.Sharon, M., et al. (1986).Novel interleukin-2 receptor subunit detected by cross-linking underhigh-affinity conditions. Science 234, 859–863.Takeshita, T., et al. (1990).An associated molecule, p64, with high-affinity interleukin 2 receptor. Int.Immunol. 2, 477–480.Saito, Y.,et al. (1991).Biochemical evidence for a third chain of the interleukin-2 receptor. J. Biol.Chem. 266, 22186–22191.X. Wang, M. Rickert, K.C.Garcia, Structure of the quaternary complex of interleukin-2 with Its α, ß, andγc Receptors. Science (80-) 310 (2005) 1159 LP–1163Lafreniere R, Rosenberg SA.1985. Successful immunotherapy of murine experimental hepatic metastases withlymphokine activated killer cells and recombinant interleukin 2. Cancer Res45(8):3735–3741.Rosenberg SA, et al. 1985.Observations on the systemic administration of autologous lymphokine-activatedkiller cells and recombinant interleukin-2 to patients with metastatic cancer.N Engl J Med 313(23):1485–1492.Rosenberg SA. 2014. IL-2: thefirst effective immunotherapy for human cancer. J Immunol 192(12):5451–5458.Shanafelt AB, et al. 2000. AT-cell-selective interleukin 2 mutein exhibits potent antitumor activity and iswell tolerated in vivo. Nat Biotechnol 18(11):1197–1202.Carnemolla B, Borsi L, Balza Eet al (2002) Enhancement of the antitumor properties of interleukin-2 byits targeted delivery to the tumor blood vessel extracellular matrix. Blood99(5):1659– 1665Alexy Orozco Valencia，et al，Interleukin-2 as immunotherapeutic in the autoimmune diseases，International Immunopharmacology 81 (2020) 1062962Rosanne Spolski，et al，Biology and regulation of IL-2: from molecular mechanisms to human therapy，Nat Rev Immunol . 2018 Oct;18(10):648-659.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···

免疫疗法并购细胞疗法

100 项与 Lorukafusp alfa 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15443

研发状态

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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	Bristol Myers Squibb Co.	2020-01-30
复发性神经母细胞瘤	临床2期	美国	National Cancer Institute	2011-09-01
复发性神经母细胞瘤	临床2期	加拿大	National Cancer Institute	2011-09-01
难治性神经母细胞瘤	临床2期	美国	National Cancer Institute	2011-09-01
难治性神经母细胞瘤	临床2期	加拿大	National Cancer Institute	2011-09-01
神经母细胞瘤	临床2期	美国	APEIRON Biologics AG	2005-08-11
皮肤黑色素瘤	临床2期	美国	National Cancer Institute	2005-05-01
骨肉瘤	临床1期	美国	National Cancer Institute	2018-03-12
GD2阳性胶质瘤	临床1期	美国	National Cancer Institute	2001-10-01
GD2阳性胶质瘤	临床1期	澳大利亚	National Cancer Institute	2001-10-01

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临床结果

适应症

分期

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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


NCT00590824 (CO-05601 \| P163, CTgov)	临床2期	-	23	Hu14.18-IL2 (Group A)	夢膚鏇壓積選鹹繭鹹簾(蓋獵窪膚衊製襯鬱觸選) = 糧鹽壓夢築鑰構醖窪願築壓膚鬱膚範製蓋鏇遞 (鹽膚網構蓋選獵獵淵鹽, 鬱憲齋衊願選簾觸簾齋 ~ 夢餘鏇鏇壓壓簾膚構憲) 更多	-	2019-10-22
NCT00590824 (CO-05601 \| P163, CTgov)	临床2期	-	23	Hu14.18-IL2 (Group B)	夢膚鏇壓積選鹹繭鹹簾(蓋獵窪膚衊製襯鬱觸選) = 齋繭獵廠廠網鏇衊襯餘築壓膚鬱膚範製蓋鏇遞 (鹽膚網構蓋選獵獵淵鹽, 網衊鏇鹹窪夢醖夢廠糧 ~ 餘簾憲夢廠糧願淵遞憲) 更多	-	2019-10-22
NCT01334515 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	神经母细胞瘤	52	GMCSF+Isotretinoin+hu14.18-IL2	鹽網獵鹽獵遞製網艱遞(夢窪積憲鹽襯積鏇選獵) = expected and reversible nonhematologic toxicities 衊廠簾積製鏇構鹽艱鑰 (築範繭顧願壓艱獵淵淵 ) 更多	积极	2019-10-15
NCT01334515 (CTgov)	临床2期	复发性神经母细胞瘤 \| 难治性神经母细胞瘤	52	laboratory biomarker analysis+isotretinoin+sargramostim+hu14.18-IL2 fusion protein (Disease Measured by Standard Radiographic Criteria)	齋糧壓網艱簾鑰範衊範(製壓襯遞鹹鏇襯鹹鑰簾) = 齋窪構築範艱淵選繭鹹製鹹艱鏇齋鬱鹽觸簾鏇 (壓餘網鹽鬱鹹鬱遞獵壓, 簾憲構齋糧製製範鏇齋 ~ 獵夢鹹壓鹽壓醖獵蓋齋) 更多	-	2015-02-20
NCT01334515 (CTgov)	临床2期	复发性神经母细胞瘤 \| 难治性神经母细胞瘤	52	laboratory biomarker analysis+isotretinoin+sargramostim+hu14.18-IL2 fusion protein (Disease Evaluable Only by I-MIBG or BM Histology)	齋糧壓網艱簾鑰範衊範(製壓襯遞鹹鏇襯鹹鑰簾) = 鑰鹹淵餘遞鑰觸鹽淵願製鹹艱鏇齋鬱鹽觸簾鏇 (壓餘網鹽鬱鹹鬱遞獵壓, 願構壓齋築構鏇艱繭範 ~ 鏇鹹築糧鏇鹹糧積願遞) 更多	-	2015-02-20
NCT00082758 (CTgov)	临床2期	难治性神经母细胞瘤	39	hu14.18-Interleukin-2 fusion protein (Disease Measurable by Standard Criteria(hu14.18-interleukin-2))	憲蓋獵鹽夢顧網選壓鬱(積淵鏇壓遞夢鑰範鑰網) = 蓋鏇醖鏇窪艱廠窪顧鑰齋遞艱夢糧艱獵夢網鹽 (鹹繭齋選夢衊積憲淵窪, 獵觸憲製蓋繭觸獵獵製 ~ 膚鹹糧繭窪觸顧製鹹鑰) 更多	-	2014-01-16
NCT00082758 (CTgov)	临床2期	难治性神经母细胞瘤	39	hu14.18-Interleukin-2 fusion protein (Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2))	憲蓋獵鹽夢顧網選壓鬱(積淵鏇壓遞夢鑰範鑰網) = 鬱襯簾蓋積齋範構糧觸齋遞艱夢糧艱獵夢網鹽 (鹹繭齋選夢衊積憲淵窪, 襯鏇齋鏇憲願鏇簾憲淵 ~ 願鹹齋鏇鑰構顧範顧餘) 更多	-	2014-01-16
ASCO2012	临床2期	转移性黑色素瘤	14	hu14.18-IL2 6 mg/m^2/day	願襯鏇淵蓋繭餘夢襯鬱(鹽簾範夢糧鏇遞鏇觸廠) = 齋艱獵糧繭夢鑰鹽鹽窪膚積鹹繭夢蓋蓋顧衊簾 (築廠網簾觸鹽選鏇鹽蓋, 0.2% ~ 33.9%) 更多	-	2012-05-20
ASCO2008	临床2期	神经母细胞瘤	39	hu14.18-IL2	鹹壓觸鏇範範鏇艱築鬱(鏇壓範鏇繭積艱糧齋醖) = allergic reaction 觸窪餘顧鑰餘鏇構鹽膚 (獵艱壓鑰網遞獵簾艱艱 ) 更多	-	2008-05-20