Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for standard risk acute lymphoblastic leukemia in children and adolescents.

开始日期2024-03-05

申办/合作机构

Samsung Medical Center

NCT04440267

/ Not yet recruiting临床2期IIT

A Prospective, Single Arm, Open Label, Clinical Trial to Evaluate the Efficacy of Acute Lymphoblastic Leukemia-Based Therapy in Treating Patients With Acute Leukemia of Ambiguous Lineage

In this prospective, single arm, open label, clinical trial, a total of 50 acute leukemia of ambiguous lineage patients will be enrolled. Patients will receive acute lymphoblastic leukemia (ALL) -based chemotherapy and are permitted to receive allogeneic hematopoietic stem cell transplantation (HSCT) after CR . Otherwise, they will finish the consolidation chemotherapy. Patients with t(9;22) will receive chemotherapy combined with tyrosine kinase inhibitors. The purpose of current study is to evaluate the clinical efficacy of ALL-based chemotherapy，effect of genetic abnormality and minimal residual disease (MRD) on prognosis in patients with acute leukemia of ambiguous lineage.

开始日期2020-06-20

申办/合作机构-

NCT06336395

/ Recruiting临床2期IIT

Ma-Spore ALL-Seq 2020: RNA-Seq and IgH/TCR-Seq to Improve Risk Assignment in Childhood, Adolescent and Young Adult Acute Lymphoblastic Leukaemia

The primary objective of this trial is to improve the overall survival rate of children and young adult with B-lineage acute lymphoblastic leukemia (B-ALL) in Singapore and Malaysia in the context of a multicenter cooperative trial using a risk-stratified therapy.

开始日期2020-03-04

申办/合作机构

National University Hospital

100 项与 L-门冬酰胺酶相关的临床结果

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100 项与 L-门冬酰胺酶相关的转化医学

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100 项与 L-门冬酰胺酶相关的专利（医药）

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项与 L-门冬酰胺酶相关的文献（医药）

2025-03-01·Current Pharmaceutical Biotechnology

Pseudomonas aeruginosa Recombinant L-asparaginase: PEGylation with Low Molecular Weight Polyethylene Glycol, Molecular Dynamics Simulation, In vitro and In vivo Serum half-life and Biochemical Characterization

Article

作者: Mahran, Eman Abdallah ; El-Nikhely, Nefertiti ; Alshamy, Rawan ; Elkewedi, Mohamed ; Nematalla, Hisham ; Saeed, Hesham

Background:Microbial L-asparaginase (L-ASNase, EC 3.5.1.1) is a pivotal biopharmaceutical drug-protein that catalyzes the hydrolysis of the non-essential amino acid L-asparagine (L-Asn) into L-aspartic acid (L-Asp) and ammonia , resulting in deplenishing the cellular L-Asn pool, which leads to the ultimate death of the L-asparagine synthetase (L-ASNS) deficient cancerous cells.Objective:This study aimed to investigate the impact of conjugating low molecular weight polyethylene glycol to recombinant P. aeruginosa L-ASNase by examining the pharmacokinetic properties, affinity towards the substrate, and enzyme stability prior to and following the reaction.Methods:The recombinant P. aeruginosa L-ASNase was affinity purified and then PEGylated by attaching polyethylene glycol (MW= 330 Da) site-specifically to the protein's N-terminus end. After which, the PEGylated L-ASNase was examined by SDS-PAGE (15%), FTIR, and UV/Vis spectrophotometry and subsequently biochemically characterized.Results:The Km and Vmax values of free P. aeruginosa rL-ASNase were determined to be 0.318 ±1.76 mM and 2915 μmol min-1and following the PEGylation, they were found to be 0.396 ±1.736 mM and 3193 μmol min-1, respectively. Polyethylene glycol (330 Da) has markedly enhanced LASNase thermostability at 37, 45, 50, and 55°C, as opposed to the free enzyme, which retained 19.5% after 1 h of incubation at 37°C. The PEGylated L-ASNase was found to be stable upon incubation with human serum for 28 h, in contrast to the sharp decline in the residual bioactivity of the free rL-ASNase after 4 h incubation. Accordingly, an in vivo study was used for validation, and it demonstrated that PEGylated rL-ASNase exhibited longer bioactivity for 24 h, while the free form's activity vanished entirely from the rats' blood sera after 8 h. Molecular dynamics simulation indicated that PEG (330 Da) has affected the hydrodynamic volume of L-ASNase and increased its structural stability. Docking analysis has explored the position of PEG with respect to binding sites and predicted a similar binding affinity to that of the free enzyme.Conclusion:For the first time, recombinant L-ASNase was modified by covalently attaching PEG (330 Da). The resultant novel proposed PEGylated rL-ASNase with remarkably increased stability and prolonged in vivo half-life duration, could be considered an alternative to mitigate the high molecular weight of PEGylation's drawbacks.

2025-01-01·Food Chemistry

L-asparaginase-mediated pH shift and carbon dot fluorescence modulation: A sensitive ratiometric method for quantifying L-asparagine in diverse potato varieties under variable storage conditions

Article

作者: El-Wekil, Mohamed M ; Alanazi, Ahmed Z. ; Barker, James ; Ali, Al-Montaser Bellah H. ; Alanazi, Ahmed Z ; Mostafa, Aya M. ; Ibrahim, Hossieny ; El-Wekil, Mohamed M. ; Alhazzani, Khalid ; Ali, Al-Montaser Bellah H ; Mostafa, Aya M ; Mahmoud, Ashraf M. ; Mahmoud, Ashraf M

This study presents a novel and selective method for the determination of l-asparagine in diverse potato varieties under various storage conditions. L-asparagine levels serve as a crucial indicator for acrylamide formation, a hazardous substance in processed potato products. The fluorometric method utilized blue-emitting CDs (B-CDs), orange-emitting CDs (O-CDs), and the enzyme L-asparaginase for ratiometric detection of L-asparagine. Upon enzymatic hydrolysis of L-asparagine by L-asparaginase, liberated ammonia induced a pH increase in the reaction medium. This pH shift enhanced the fluorescence of B-CDs while simultaneously decreasing that of O-CDs, enabling sensitive and selective L-asparagine quantification. Comprehensive characterization of the CDs was performed using various spectroscopic techniques and transmission electron microscopy. The method demonstrated excellent sensitivity (LOD = 0.31 μM) and a wide linear range (1.0-50.0 μM). When the method was applied to potato samples, high recovery values (98.00-100.33 %) with low relative standard deviations (RSDs) were achieved, confirming the accuracy and precision of the method. The approach was employed to determine L-asparagine levels in three potato varieties (Lady Rosetta, Spunta, and Nicola) under different storage temperatures and durations. This method provides a valuable tool for monitoring L-asparagine content in potatoes, potentially aiding in the mitigation of acrylamide formation during processing. The robust performance and simplicity of the proposed technique make it suitable for routine analysis in both research and industrial applications within the potato industry.

2025-01-01·Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

pH-Sensitive blue and red N-CDs for L-asparaginase quantification in complex biological matrices

Article

作者: El-Wekil, Mohamed M ; Mostafa, Aya M ; Barker, James ; Bellah H Ali, Al-Montaser ; Alhazzani, Khalid ; Mostafa, Aya M. ; Ibrahim, Hossieny ; El-Wekil, Mohamed M. ; Alanazi, Ahmed Z ; Bellah H. Ali, Al-Montaser ; Mahmoud, Ashraf M ; Mahmoud, Ashraf M. ; Alanazi, Ahmed Z.

A novel fluorometric method for the determination of L-asparaginase, an enzyme crucial in cancer therapy and food industry applications, is presented. This sensitive and selective approach utilizes L-asparagine and two pH-sensitive carbon dots (blue-N-CDs and red-N-CDs) as probes. The interaction between L-asparagine and L-asparaginase liberates ammonia, causing an increase in pH. This pH change simultaneously decreases the fluorescence of blue-N-CDs while enhancing the emission of red-N-CDs, enabling ratiometric detection of L-asparaginase. Comprehensive characterization of both carbon dots and investigation of their response mechanism towards L-asparaginase were conducted using ultraviolet-visible spectrophotometry, fluorescence spectroscopy, and transmission electron microscopy (TEM) imaging techniques. The designed approach demonstrates outstanding linearity (20 to 2000 U L^-1) and a low detection limit (6.95 U L^-1) for L-asparaginase quantification. Moreover, when tested to human serum samples, the detection system exhibits outstanding selectivity and high recovery rates (96.15% to 99.75%) with low standard deviation, underscoring its suitability for practical implementation in clinical diagnostics.

项与 L-门冬酰胺酶相关的新闻（医药）

2024-12-06

·学术经纬

Cancer Discovery｜儿童急性T淋巴细胞白血病的临床特征与高危突变

撰文 | 尹彤责编 | 周叶斌急性T淋巴细胞白血病（T-ALL）是儿童最常见的血液系统肿瘤之一。其中γδ T-ALL是一个较少研究的亚型，其肿瘤细胞表面表达由γ链和δ链组成的T细胞受体（TCR），约占全部T-ALL病例的10%。既往研究提示，该亚型可能面临更差的治疗效果和更高的复发风险。由于缺乏大规模针对γδ T-ALL的研究，其临床特征和发病机制仍不清楚。虽然近年来通过基因组学研究取得了一些进展，但这些研究纳入的γδ T-ALL病例较少，且缺乏对非编码区等基因组特征的分析，因此亟需进行更全面、深入的研究。近日，以圣裘德儿童研究医院 Charles G. Mullighan 和 Hiroto Inaba 团队牵头的多国联合团队在 Cancer Discovery 发表了题为 Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk 的文章。该研究基于200例γδ T-ALL的临床和基因组数据，揭示了发病年龄<3岁、诱导治疗后MRD≥1%和STAG2/LMO2突变是儿童γδ T-ALL的高危因素，进而筛选了针对此类患者有效的治疗策略。本研究纳入了由13项临床研究组成的多国合作组的200例25岁以下的γδ T-ALL患者，以及1,067例根据治疗方案匹配的非γδ T-ALL对照病例。研究发现，γδ T-ALL患者总体上表现出较差的预后，诊断年龄更小，且治疗后的应答更差，表现为在诱导治疗和巩固治疗后都有更高的微小残留病变（measurable residual disease，MRD）水平，需要进行造血干细胞移植的比例更高，且原发病或治疗副作用造成的死亡率更高。诊断年龄小于3岁的γδ T-ALL患者，其5年无事件生存率（event-free survival，EFS）仅为33%，总生存率（overall survival，OS）仅为49%，显著低于诊断年龄≥3岁的γδ T-ALL患者或非γδ T-ALL患者。此外，诱导治疗结束时（end of induction，EOI），MRD≥1%的患者在所有年龄段的生存率均显著低于MRD<1%的患者。这些数据表明诊断年龄 <3岁和 EOI 时 MRD≥1% 是提示 γδ T-ALL 患儿不良预后的高危因素，因此这些高风险患者可能需要优化的治疗方案。此外，研究发现，γδ T-ALL患者的复发主要局限于骨髓（骨髓复发率高达91.3%），而非γδ T-ALL患者中枢神经系统复发更常见。研究设计和患者临床结局：（A）研究方案，（B）γδ T-ALL患者与非γδ T-ALL患者的生存率对比，（C/D）γδ T-ALL患者中诊断年龄和EOI时MRD水平对生存率的影响结合全基因组测序（whole genome sequencing，WGS）、RNA测序和HiChIP等技术，研究者对γδ T-ALL患者的基因变异进行了分型，并解析了突变导致的疾病机制。γδ T-ALL患者与非γδ T-ALL患者相比具有独特的基因型分布。STAG2/LMO2双突变是γδ T-ALL患者特征性变异之一，所有纳入研究的该亚型γδ T-ALL患儿的诊断年龄都小于3岁，且与其他类型患者相比生存期显著较短。进一步研究表明STAG2/LMO2双突变患者中最常见的变异类型是LMO2::STAG2重排，导致STAG2失活和LMO2过度激活。STAG2是黏着复合物（cohesin complex）的重要组分，参与染色质空间折叠以形成拓扑相关结构域（topologically associating domain，TAD），进而通过增强子-启动子相互作用调控基因正常表达。通过构建STAG2缺失和过表达的细胞模型，并进行RNA-seq和H3K27ac ChIP-seq分析，研究者证明了STAG2失活将导致TAD结构异常，严重破坏T细胞分化相关基因表达，导致白血病的发生。此外，研究还发现了其他γδ T-ALL特异性基因分型，如LMO2-γδ样、超二倍体T-ALL伴重现性染色体增加、TLX3重排和PICALM::MLLT10融合等，这些亚型γδ T-ALL患者具有各自不同的临床特征。 γδ T-ALL基因分型和临床特征：（A）参考所有T-ALL基因组数据对γδ T-ALL进行基因分型，（B）不同基因型在γδ T-ALL与非γδ T-ALL患者中的分布，（D）γδ T-ALL患者不同基因型与诊断年龄的关系，（E）不同基因型γδ T-ALL患者的生存曲线最后，研究者通过高通量药物筛选探索了潜在的治疗策略。PARP抑制剂talazoparib和组蛋白去乙酰化酶抑制剂vorinostat是对STAG2/LMO2 γδT-ALL细胞具有显著杀伤作用的药物，其中PARP抑制剂靶向STAG2失活造成的DNA复制缺陷，使双链DNA断裂积累并诱导细胞死亡。在患者来源的异种移植模型（PDX）中，talazoparib 和 vorinostat 都可以有效地抵抗肿瘤生长。其他有效的药物包括nelarabine和L-门冬酰胺酶等，这些药物都已经被用于T-ALL或其他肿瘤的临床研究或治疗。此发现为高风险的γδ T-ALL患儿提供了一种潜在的精准治疗策略。针对talazoparib（Tal）和vorinostat（Vor）的临床前试验表明两种药物均能够显著抑制PDX肿瘤细胞的生长总之，本研究首次全面探讨了儿童γδ T-ALL的临床特征和基因分型，并揭示了高危突变的致病机制及潜在的治疗策略。研究明确了诊断年龄和MRD水平对患者预后的关键作用，并揭示了高危患儿STAG2失活对染色质结构和基因表达具有深远影响。更重要的是，本研究提出了 PARP 抑制剂等可做为靶向 STAG2/LMO2 亚型的潜在治疗策略，这些成果加深了对儿童γδ T-ALL的认识，也为未来γδ T-ALL患儿的风险分层和个体化治疗开发提供了重要参考。撰文责编制作排版 | Sheila 校对 | uu 延伸阅读儿童T细胞急性淋巴细胞白血病的多组学分析竺晓凡/张英驰团队揭示儿童T-ALL癌细胞克隆演化模式及耐药新机制 *本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系shiyu@curekids.cn。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。 ▼滑动查看更多▼ 原文摘要（Abstract） Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition. DOI: 10.1158/2159-8290.CD-23-1452 👇点击此处，直达原文

细胞疗法临床结果免疫疗法临床研究信使RNA

2024-01-09

·Science Daily

The hidden identity of leukemia

Researchers used various sequencing technologies to explore the molecular characteristics of myeloid/natural killer cell precursor acute leukemia (MNKPL). They observed activation of the NOTCH1 and RUNX3 genes, with lower expression of the BCL11B gene. MNKPL cells were also highly sensitive to a drug called L-asparaginase. Collectively, these qualities make MNKPL distinct from other leukemia types. These insights will assist with more accurate clinical diagnoses and therapeutic development for MNKPL. Leukemia is a common term used to refer to a form of blood cancer. However, there are different types of leukemia depending on the cell type involved. One unique form is myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL). Because of its rarity, there is no consensus on the specific characteristics needed to clinically identify this disease. In a recent article published in Science Advances, a team led by researchers at Tokyo Medical and Dental University (TMDU) used various approaches to better assess the molecular pro drug sensitivity characteristics of MNKPL. MNKPL was only first proposed as a leukemia subtype in 1997. Extramedullary involvement is one of the hallmarks of MNKPL. It is prevalent in East Asian countries. Although the immunological phenotype of MNKPL was explored previously, a full genetic characterization of this cancer type had not been performed. These details would help support more accurate diagnoses for patients, which would lead to more appropriate therapeutic decisions. Therefore, the TMDU group aimed to investigate MNKPL on a single-cell level. "A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease," says Dr. Akira Nishimura, lead author of the study. The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signaling pathways at the RNA level, and examine any unique DNA methylation patterns. "Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia," explains Dr. Masatoshi Takagi, senior author. "Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B." Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type. The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs. "We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease," says Dr. Nishimura. "Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukemia." Overall, the robust and comprehensive analysis performed in this study provides crucial molecular details for characterizing MNKPL. This work will undoubtedly help clinicians more effectively diagnose MNKPL and choice of therapeutic option. Additionally, this work provides data that will assist with novel therapeutic target identification and drug development in this leukemia.

细胞疗法

2023-06-09

·生物制品圈

最新进展！北京大学高卫平团队研究发现治疗恶性肿瘤新策略

导读：L-天冬酰胺酶（ASP）以其在治疗血液系统恶性肿瘤方面的出色功效而闻名。不幸的是，ASP的内在缺陷，即免疫原性高，毒性严重，半衰期短，稳定性差，限制了其临床应用。ASP的聚乙二醇偶联（聚乙二醇）偶联（聚乙二醇化）是解决这些问题的有效策略，但由于复杂的化学合成程序，偶联后ASP活性降低以及人类中预先存在的抗PEG抗体，它在临床应用中并不理想。6月4日，北京大学高卫平团队在《Advanced Science》在线发表题为“Thermoresponsive Polypeptide Fused L-Asparaginase with Mitigated Immunogenicity and Enhanced Efficacy in Treating Hematologic Malignancies”的研究论文，该研究通过基因工程设计了一种类弹性蛋白多肽（ELP）融合的ASP（ASP-ELP），这是一种由AlphaFold2预测的核壳结构四聚体，能够克服ASP和PEG-ASP的局限性。https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202300469研究背景 01 血液系统恶性肿瘤，主要包括白血病、淋巴瘤和多发性骨髓瘤，预后不良，死亡率高。在过去的二十年中，血液恶性肿瘤的药物开发已经从化疗转向生物疗法，如单克隆抗体、免疫检查点抑制剂和嵌合抗原受体 T 细胞。然而，由于脱靶效应，这些疗法遇到了巨大的挑战，抗原逃逸、免疫相关不良事件和免疫治疗耐药性。L-天冬酰胺酶（ASP）是最具标志性的疗法之一，30多年来一直主导着血液系统恶性肿瘤的治疗。ASP可以通过催化L-天冬酰胺的分解来诱导癌细胞的凋亡，这对于它们的生长至关重要。不幸的是，由于ASP的免疫原性高、毒性严重、半衰期短、稳定性差，通常需要多次大剂量给药才能达到足够的治疗效果，这不可避免地会引起严重的副作用，如超敏反应、胰腺炎、肝脂肪变性、肝硬化和凝血障碍。ASP的聚乙二醇化已被证明是克服这些问题的有效策略。事实上，PEG-ASP，商业名称Oncaspar，于2006年被美国食品和药物管理局（FDA）批准为急性淋巴细胞白血病（ALL）的一线治疗药物。然而，最近的研究发现，由于PEG在食品、化妆品和药品中的应用，预先存在的抗PEG抗体在人类中广泛存在，这可能诱发血液清除加速（ABC）现象和严重的超敏反应，并降低其临床疗效。因此，研究人员试图将聚（羧基甜菜碱）（PCB），谷氨酸和赖氨酸（EK）肽或聚-（L）-脯氨酸（PLP）与ASP偶联，而不是PEG。然而，化学合成的固有缺点，包括复杂的合成过程、缺乏可重复性、低产率和高成本，使得这些ASP-聚合物偶联物的临床应用极其困难。研究进展 02 先前的研究发现，由Val-Pro-Gly-Val-Gly重复组成的弹性蛋白样多肽（ELP）可以在注射后迅速形成具有零级释放动力学的缓释库，从而延长药物半衰期，避免高浓度诱导的副作用，提高最大耐受剂量（MTD），提高干扰素-α的治疗效果。受此启发，我们假设ASP的ELP融合将产生AlphaFold2预测的核壳结构四聚体，通过包裹ASP的抗原表位来降低ASP的免疫原性。我们进一步推断，ASP-ELP独特的热敏性应该在腹膜内注射时形成缓释药物库，从而改善药代动力学，降低全身毒性并增强抗肿瘤功效。为了确认ASP-ELP是否可以替代PEG-ASP和ASP作为更有前途的血液系统恶性肿瘤治疗剂，我们通过活性保留和稳定性的体外研究以及MTD，药代动力学，免疫原性，毒性和抗肿瘤作用的体内研究来测试它们的性能。用于治疗血液恶性肿瘤的ASP-ELP核壳结构四聚体的AI辅助设计示意图。A）ASP-ELP的生物合成和结构预测。将ASP片段遗传融合到ELP的N末端以构建ASP-ELP质粒，然后在大肠杆菌（大肠杆菌）中过表达。利用AlphaFold2获得同源四聚体复合物结构，预测ASP-ELP与ASP-ELP之间的相互作用。ELP链缠绕在ASP的四聚体表面，形成核壳结构，掩盖ASP的抗原表位，赋予ASP-ELP低免疫原性和高稳定性。B）ASP-ELP独特的热敏性使得在注射后形成具有零级释放动力学的原位缓释库成为可能，从而增加MTD，增强药代动力学，减轻免疫原性，提高疗效并降低毒性。相反，高免疫原性ASP瞬间分布到体循环系统中会产生高浓度ASP，诱导免疫毒性和剂量相关毒性，导致药代动力学和疗效差。研究成果 03 总之，我们通过对弹性蛋白样多肽（ELP）融合ASP（ASP-ELP）进行基因工程改造，这是一种由AlphaFold2预测的核壳结构四聚体，以克服ASP和PEG-ASP的局限性。值得注意的是，ASP-ELP独特的热敏性使得注射后能够长时间原位形成具有零阶释放动力学的缓释库。体外和体内研究表明，与ASP和PEG-ASP相比，ASP-ELP具有更高的活性保留，改善的稳定性，延长的半衰期，减轻免疫原性，降低毒性和增强的功效。事实上，在白血病或淋巴瘤小鼠细胞系衍生异种移植（CDX）模型中的ASP-ELP治疗显示出有效的抗癌作用，显着延长了生存期。研究结果还表明，人工智能（AI）辅助的基因工程在设计蛋白质-多肽偶联物方面具有指导意义，并可能为开发下一代生物制剂以增强癌症治疗铺平道路。参考资料：https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202300469识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

免疫疗法

100 项与 L-门冬酰胺酶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	L01XX02	DB00023

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
急性和慢性白血病	韩国	Kyowa Kirin Korea Co., Ltd.	1993-03-19
急性淋巴细胞白血病	日本	Kyowa Kirin Co., Ltd.	1971-06-25
淋巴瘤	日本	Kyowa Kirin Co., Ltd.	1971-06-25

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临床结果

适应症

分期

评价

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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


EHA2021	N/A	急性淋巴细胞白血病	316	L-asparaginase	(構廠觸壓餘範鏇積衊顧) = 齋鹽鹹蓋醖餘網醖繭淵糧壓鏇醖遞網壓製選遞 (艱網遞構醖憲獵餘衊網 ) 更多	-	2021-06-09
ISTH2020	N/A	急性淋巴细胞白血病	-	L-Asparaginase	選構獵觸簾簾鏇觸衊衊(鏇遞範積廠築壓憲憲鹽) = 鏇遞餘繭選遞齋蓋膚築鹽遞夢簾憲衊鏇蓋顧鹽 (鑰鏇壓餘醖獵鑰壓構築 ) 更多	-	2020-07-12
Peking University Cancer Hospital (ICML2017)	N/A	结外NK-T细胞淋巴瘤一线	196	L-asparaginase (CHOP-like)	積範鏇艱餘廠願範鬱壓(夢繭繭鑰鹹鏇齋廠鹹蓋) = 簾網壓壓窪觸鑰蓋鹽壓艱憲願鹹鏇餘顧願膚膚 (襯獵築鏇簾膚繭廠構壓 ) 更多	积极	2017-06-07
Peking University Cancer Hospital (ICML2017)	N/A	结外NK-T细胞淋巴瘤一线	196	L-asparaginase (CHOP-L)	積範鏇艱餘廠願範鬱壓(夢繭繭鑰鹹鏇齋廠鹹蓋) = 窪鑰糧淵憲網壓夢築鹹艱憲願鹹鏇餘顧願膚膚 (襯獵築鏇簾膚繭廠構壓 ) 更多	积极	2017-06-07
ICML2015	临床1/2期	难治性弥漫性大 B 细胞淋巴瘤 MYC-rearranged \| ki67	9	l-asparaginase	鹽壓範醖鏇觸繭糧獵顧(夢願醖鑰襯製遞艱鏇構) = Grade 3 hepatic toxicity occurred in one patient during the first cycle 製繭醖鬱築積鹽鑰鹽範 (齋觸遞網鹽築壓簾選窪 ) 更多	积极	2015-06-09
AACR2010	N/A	肥胖一线	7	L-asparaginase (Lean subjects)	鏇鏇廠艱艱淵廠選獵獵(範蓋憲範製築鏇淵壓鑰) = 襯簾膚齋淵襯選遞夢觸願衊窪簾築鏇遞積構獵 (鏇製壓襯襯壓齋膚鹹鑰 ) 更多	-	2010-04-15
AACR2010	N/A	肥胖一线	7	L-asparaginase (Obese subjects)	鏇鏇廠艱艱淵廠選獵獵(範蓋憲範製築鏇淵壓鑰) = 製鬱壓鑰願膚蓋鹹醖糧願衊窪簾築鏇遞積構獵 (鏇製壓襯襯壓齋膚鹹鑰 ) 更多	-	2010-04-15