Current Research in Translational Medicine最新文献_第4页

Green solvent-based synthesis of diclofenac diethylamine-loaded PCL nanoparticles for sustained drug delivery 绿色溶剂基合成双氯芬酸二乙胺负载PCL纳米颗粒的持续给药

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-17 DOI: 10.1016/j.retram.2025.103529

Soolafa Al Soliman , Zaki Ali Ajji , Antoun Al-Laham

Background

Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), has demonstrated promising antitumor properties; however, its clinical application is limited by systemic toxicity. Encapsulation in biodegradable polymeric nanoparticles offers a strategy to enhance therapeutic efficacy while minimizing adverse effects. Nevertheless, the use of toxic organic solvents in nanoparticle fabrication remains a significant challenge.

Objective

This study aimed to develop and characterize diclofenac diethylamine-loaded polycaprolactone (PCL) nanoparticles using green solvents and to compare two preparation methods-emulsification solvent evaporation/extraction and spontaneous emulsification solvent diffusion-for producing diclofenac-loaded nanoparticles with potential applications in tumor therapy.

Methods

Diclofenac diethylamine-loaded PCL nanoparticles were prepared using both methods, employing a novel green solvent system. The nanoparticles were characterized in terms of size, polydispersity index (PDI), zeta potential, morphology, and encapsulation efficiency. In vitro drug release profiles were evaluated and fitted to kinetic models.

Results

The developed diclofenac diethylamine-loaded PCL nanoparticles exhibited a mean diameter below 200 nm, a monodisperse population, and a negative surface charge. Both preparation methods achieved high encapsulation efficiency and prolonged, diffusion-controlled drug release. The spontaneous solvent diffusion method provided slightly better control over particle size.

Conclusion

These nanoparticles are well-suited for cancer therapy, offering sustained drug release, enhanced safety due to the use of green solvents, and robust physicochemical stability. The findings support their potential as an innovative, effective, and safe delivery system for antitumoral applications.

双氯芬酸是一种非甾体抗炎药（NSAID），具有良好的抗肿瘤特性；然而，其临床应用受到全身毒性的限制。包封在可生物降解的聚合物纳米颗粒提供了一种策略，以提高治疗效果，同时尽量减少不良反应。然而，在纳米颗粒制造中使用有毒有机溶剂仍然是一个重大挑战。目的利用绿色溶剂制备双氯芬酸二乙胺负载的聚己内酯（PCL）纳米颗粒，并对其进行表征，比较乳化溶剂蒸发/萃取和自发乳化溶剂扩散两种制备双氯芬酸负载纳米颗粒的方法。方法采用新型绿色溶剂体系，采用两种方法制备双氯芬酸二乙胺负载PCL纳米颗粒。从尺寸、多分散性指数（PDI）、zeta电位、形貌和包封效率等方面对纳米颗粒进行了表征。体外药物释放曲线进行评估，并拟合动力学模型。结果制备的双氯芬酸二乙胺负载PCL纳米粒子平均直径小于200 nm，粒子群单分散，表面带负电荷。两种制备方法均具有较高的包封效率和较长的扩散控制药物释放时间。自发溶剂扩散法对粒径的控制稍好一些。结论这些纳米颗粒具有药物缓释、使用绿色溶剂增强安全性和良好的物理化学稳定性等优点，非常适合用于癌症治疗。这些发现支持了它们作为一种创新、有效和安全的抗肿瘤给药系统的潜力。

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引用次数: 0

CC486 as a safe and effective bridge to transplant in MDS-del5q with transfusion-dependent anemia following lenalidomide relapse: A case report 来那度胺复发后输血依赖性贫血的MDS-del5q患者，CC486作为安全有效的移植桥梁：1例报告

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-09 DOI: 10.1016/j.retram.2025.103528

G. Scorpio , A. Francesio , S. Piemontese , A. Acerbis , S. Mastaglio , F. Giglio , G.M. Bergonzi , L. Lazzari , A. Ruggeri , A. Bruno , S. Marktel , M.T. Lupo-Stanghellini , A. Assanelli , M. Bernardi , L. Vago , F. Ciceri , E. Diral

引用次数: 0

The immunobiological functions and therapeutic applications of interleukin-17 family in cancer 白细胞介素-17家族在肿瘤中的免疫生物学功能及治疗应用

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-02 DOI: 10.1016/j.retram.2025.103527

Nasrin Mansuri , Asma'a H. Mohamed , Marya Ahsan , Sana Abdul-Jabbar Ali , Mohammed Ansar Qureshi , Waleed A Aldhaaban , Ayaz Khurram Mallick , Muataz Elsiddig Dafaalla Mohammed , Fuzail Ahmad , Irshad Ahmad , Mohammad Chand Jamali , Alaa Shafie

Interleukin-17 (IL-17) family cytokines play a pivotal role in immune responses and inflammatory processes, significantly impacting various physiological and pathological conditions. This review explores the immunobiological functions of IL-17, focusing on its diverse cellular sources, including T helper 17 (Th17) cells, γδ T cells, innate lymphoid cells (ILCs), neutrophils, and natural killer T (NKT) cells, and signaling pathways. Special attention is given to IL-17 involvement in cancer, where it exhibits both pro-tumorigenic and anti-tumorigenic effects, influencing tumor proliferation, angiogenesis, metastasis, and drug resistance through various signaling cascades such as JAK/STAT, NF-κB, and PI3K/AKT. Understanding these mechanisms highlights IL-17 as a potential therapeutic target for modulating immune responses and improving cancer treatments.

白细胞介素-17 （IL-17）家族细胞因子在免疫反应和炎症过程中起关键作用，显著影响各种生理和病理状况。本文综述了IL-17的免疫生物学功能，重点介绍了其不同的细胞来源，包括T辅助17 （Th17）细胞、γδ T细胞、先天淋巴样细胞（ILCs）、中性粒细胞和自然杀伤T （NKT）细胞，以及信号通路。特别关注IL-17在癌症中的参与，它表现出促肿瘤和抗肿瘤作用，通过各种信号级联如JAK/STAT、NF-κB和PI3K/AKT影响肿瘤增殖、血管生成、转移和耐药。了解这些机制凸显了IL-17作为调节免疫反应和改善癌症治疗的潜在治疗靶点。

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引用次数: 0

Enhancing Alzheimer's disease prediction using random forest: A novel framework combining backward feature elimination and ant colony optimization 利用随机森林增强阿尔茨海默病预测：一种结合反向特征消除和蚁群优化的新框架

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-01 DOI: 10.1016/j.retram.2025.103526

Afeez A. Soladoye , Nicholas Aderinto , Bolaji A. Omodunbi , Adebimpe O. Esan , Ibrahim A. Adeyanju , David B. Olawade

Background

Alzheimer's disease (AD) represents a significant global health challenge due to its increasing prevalence and the limitations of current diagnostic approaches. Early detection is crucial as pathological changes occur 10-15 years before clinical symptoms manifest, yet current diagnostic methods typically identify the disease at moderate to advanced stages. Machine learning techniques offer promising solutions for early prediction, but face challenges related to feature selection and hyperparameter optimization.

Objective

To develop an enhanced predictive model for Alzheimer's disease by integrating advanced feature selection techniques with nature-inspired hyperparameter optimization for Random Forest classifiers while ensuring robust validation and statistical significance testing.

Methods

This study employed three feature selection techniques (Whale Optimization Algorithm, Artificial Bee Colony, and Backward Elimination Feature Selection) and two hyperparameter optimization algorithms (Artificial Ant Colony Optimization and Bald Eagle Search) to improve Random Forest model performance. A dataset comprising 2,149 instances with 34 features was preprocessed using MinMax normalization and Synthetic Minority Oversampling Technique (SMOTE) applied only to training data to prevent data leakage. Statistical significance testing using McNemar's test was conducted to compare model performances. Model performance was evaluated using accuracy, precision, recall, F1-score, and AUC with confidence intervals calculated using bootstrap sampling.

Results

The combination of Backward Elimination Feature Selection with Artificial Ant Colony Optimization achieved the highest performance (95% accuracy ± 1.2%, 95% precision ± 1.1%, 94% recall ± 1.3%, 95% F1-score ± 1.0%, 98% AUC ± 0.8%), outperforming other methodological combinations and conventional machine learning algorithms with statistically significant improvements (p < 0.001). This approach identified 26 significant features associated with Alzheimer's disease. Additionally, nature-inspired optimization algorithms demonstrated substantial computational efficiency advantages over empirical approaches (18 minutes versus 133 minutes).

Conclusion

The integration of advanced feature selection with nature-inspired hyperparameter optimization enhances Alzheimer's disease prediction accuracy while improving computational efficiency. However, external validation on independent datasets and prospective clinical studies are needed to establish real-world utility. This methodological framework offers promising applications for early diagnosis and intervention planning, with potential extensions to other complex medical prediction tasks.

阿尔茨海默病（AD）由于其日益增加的患病率和当前诊断方法的局限性，代表了一个重大的全球健康挑战。早期发现是至关重要的，因为病理变化发生在临床症状出现前10-15年，但目前的诊断方法通常在中度至晚期阶段识别疾病。机器学习技术为早期预测提供了有希望的解决方案，但面临着与特征选择和超参数优化相关的挑战。目的在保证鲁棒性验证和统计显著性检验的前提下，将先进的特征选择技术与随机森林分类器的自然启发超参数优化相结合，建立增强的阿尔茨海默病预测模型。方法采用鲸类优化算法、人工蜂群算法和反向消除特征选择三种特征选择技术和人工蚁群优化算法和秃鹰搜索两种超参数优化算法来提高随机森林模型的性能。使用MinMax归一化和合成少数派过采样技术（SMOTE）对包含2149个实例和34个特征的数据集进行预处理，该技术仅应用于训练数据，以防止数据泄漏。采用McNemar检验进行统计显著性检验，比较模型性能。使用准确度、精密度、召回率、f1分数和AUC对模型性能进行评估，并使用自举抽样计算置信区间。结果后向消除特征选择与人工蚁群优化相结合获得了最高的性能（95%正确率±1.2%，95%精密度±1.1%，94%召回率±1.3%，95% f1评分±1.0%,98% AUC±0.8%），优于其他方法组合和传统机器学习算法，具有统计学意义(p <；0.001)。该方法确定了与阿尔茨海默病相关的26个重要特征。此外，与经验方法相比，受自然启发的优化算法显示出显著的计算效率优势（18分钟vs 133分钟）。结论将高级特征选择与自然启发的超参数优化相结合，提高了阿尔茨海默病预测的准确性，同时提高了计算效率。然而，需要对独立数据集和前瞻性临床研究进行外部验证才能建立实际效用。这种方法框架为早期诊断和干预计划提供了有希望的应用，并有可能扩展到其他复杂的医学预测任务。

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引用次数: 0

Assessment of pre- and post-transplant concentrations of citrulline, zonulin, and calprotectin in children undergoing allogeneic hematopoietic cell transplantation 接受同种异体造血细胞移植的儿童移植前后瓜氨酸、zonulin和钙保护蛋白浓度的评估

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-06-19 DOI: 10.1016/j.retram.2025.103525

Pejman Rohani , Faezeh Tejareh , Amir Ali Hamidieh , Maryam Behfar , Mohammad Hassan Sohouli

Background

Allogeneic hematopoietic cell transplantation (allo-HCT) is a life-saving treatment for pediatric patients but is often associated with severe gastrointestinal complications. Identifying reliable biomarkers of gut integrity and inflammation is crucial for early detection and management of these issues. This study evaluates pre- and post-transplant levels of citrulline, zonulin, and calprotectin in pediatric allo-HCT patients.

Methods

A prospective cohort study was conducted on 100 pediatric patients at the Children’s Hospital from 2023 to 2025. Citrulline, zonulin, and calprotectin levels were measured at baseline (pre-transplant), 3 months, and 6 months post-transplant.

Results

Calprotectin and zonulin levels peaked at 3 months post-transplant (calprotectin: 123 ± 40 µg/g, p < 0.001; zonulin: 90.69 ± 20.32 ng/mL, p = 0.001) and declined by 6 months (calprotectin: 90.05 ± 30.27 µg/g; zonulin: 70.74 ± 15.38 ng/mL). Citrulline levels decreased from 25.49 ± 8.22 µM at baseline to 20.39 ± 5.52 µM at 6 months (p = 0.004). Elevated calprotectin and zonulin levels were strongly associated with severe GVHD (Grade III-IV: calprotectin 153.25 ± 51.81 µg/g, p = 0.001; zonulin 110.05 ± 25.33 ng/mL, p = 0.002) and higher grades of diarrhea and mucositis. Patients with obesity (BMI > 30) had significantly higher biomarker levels. Multiple hospital readmissions were also associated with elevated biomarker levels (p < 0.05).

Conclusion

Citrulline, zonulin, and calprotectin are promising biomarkers for assessing GI toxicity and inflammation in pediatric allo-HCT recipients. Their levels correlate with the severity of post-transplant complications, nutritional status, and clinical outcomes.

背景：同种异体造血细胞移植（allogeneic hematopoietic cell transplantation, allo-HCT）是一种挽救儿科患者生命的治疗方法，但通常伴有严重的胃肠道并发症。确定可靠的肠道完整性和炎症生物标志物对于这些问题的早期发现和管理至关重要。本研究评估了移植前和移植后儿科同种异体hct患者瓜氨酸、zonulin和钙保护蛋白的水平。方法对2023年至2025年在儿童医院就诊的100例儿童患者进行前瞻性队列研究。在基线（移植前）、移植后3个月和6个月测量瓜氨酸、zonulin和钙保护蛋白水平。结果钙保护蛋白和zonulin水平在移植后3个月达到峰值(钙保护蛋白：123±40µg/g， p <；0.001;zonulin: 90.69±20.32 ng/mL, p = 0.001)， 6个月后下降(calprotectin: 90.05±30.27µg/g；zonulin: 70.74±15.38 ng/mL)。瓜氨酸水平从基线时的25.49±8.22µM下降到6个月时的20.39±5.52µM （p = 0.004）。钙保护蛋白和zonulin水平升高与严重GVHD密切相关(III-IV级：钙保护蛋白153.25±51.81µg/g, p = 0.001；zonulin（110.05±25.33 ng/mL, p = 0.002）及较高程度的腹泻和黏膜炎。肥胖患者(BMI >；30)的生物标志物水平显著升高。多次再入院也与生物标志物水平升高有关(p <；0.05)。结论瓜氨酸、zonulin和钙保护蛋白是评估儿童同种异体hct受体胃肠道毒性和炎症的有希望的生物标志物。它们的水平与移植后并发症的严重程度、营养状况和临床结果相关。

{"title":"Assessment of pre- and post-transplant concentrations of citrulline, zonulin, and calprotectin in children undergoing allogeneic hematopoietic cell transplantation","authors":"Pejman Rohani , Faezeh Tejareh , Amir Ali Hamidieh , Maryam Behfar , Mohammad Hassan Sohouli","doi":"10.1016/j.retram.2025.103525","DOIUrl":"10.1016/j.retram.2025.103525","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic cell transplantation (allo-HCT) is a life-saving treatment for pediatric patients but is often associated with severe gastrointestinal complications. Identifying reliable biomarkers of gut integrity and inflammation is crucial for early detection and management of these issues. This study evaluates pre- and post-transplant levels of citrulline, zonulin, and calprotectin in pediatric allo-HCT patients.</div></div><div><h3>Methods</h3><div>A prospective cohort study was conducted on 100 pediatric patients at the Children’s Hospital from 2023 to 2025. Citrulline, zonulin, and calprotectin levels were measured at baseline (pre-transplant), 3 months, and 6 months post-transplant.</div></div><div><h3>Results</h3><div>Calprotectin and zonulin levels peaked at 3 months post-transplant (calprotectin: 123 ± 40 µg/g, <em>p</em> < 0.001; zonulin: 90.69 ± 20.32 ng/mL, <em>p</em> = 0.001) and declined by 6 months (calprotectin: 90.05 ± 30.27 µg/g; zonulin: 70.74 ± 15.38 ng/mL). Citrulline levels decreased from 25.49 ± 8.22 µM at baseline to 20.39 ± 5.52 µM at 6 months (<em>p</em> = 0.004). Elevated calprotectin and zonulin levels were strongly associated with severe GVHD (Grade III-IV: calprotectin 153.25 ± 51.81 µg/g, <em>p</em> = 0.001; zonulin 110.05 ± 25.33 ng/mL, <em>p</em> = 0.002) and higher grades of diarrhea and mucositis. Patients with obesity (BMI > 30) had significantly higher biomarker levels. Multiple hospital readmissions were also associated with elevated biomarker levels (<em>p</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Citrulline, zonulin, and calprotectin are promising biomarkers for assessing GI toxicity and inflammation in pediatric allo-HCT recipients. Their levels correlate with the severity of post-transplant complications, nutritional status, and clinical outcomes.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 4","pages":"Article 103525"},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Infections in VEXAS syndrome: a systematic review of the literature VEXAS综合征的感染：文献的系统回顾

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-06-18 DOI: 10.1016/j.retram.2025.103524

Syed B Ali , Carmelo Gurnari

Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease for which chronic immunosuppression is needed. Opportunistic infections are common; however, a clear prophylaxis regimen is not defined.

A systematic review of the literature was undertaken. Six publications with 123 patients were evaluated. Of 86 patients with demographic data; most were males (n = 85, 98.8 %) and median age was 73 years. UBA1 mutational status was reported in 80 patients: p.Met41Thr (n = 43, 53.8 %), p.Met41Val (n = 17, 21.3 %) and p.Met41Leu (n = 12, 15.0 %) were most common. In these patients, 48 (60 %) had underlying myelodysplastic syndrome.

Many of the patients had multiple hospitalizations. Infections were reported as follows: COVID19 (n = 20), Pneumocystis jiroveci pneumonia (PJP) (n = 16), nontuberculous mycobacterium (NTM) species (n = 16), Enterobacteriaceae species (n = 14), Legionella species (n = 13), Varicella Zoster virus (n = 11) and Herpes Simplex Virus (n = 8) infections, respectively.

Daily prednisolone dose was at, or greater than 10 mg and overall median long term steroid treatment duration was 3.1 years. Notably, for NTM the median daily prednisolone dose was 12.5 mg. Median prednisolone dosing for PJP was only reported in one of the publications, comprising six patients, at 17 mg per day. Where data was available, 45 of the 95 patients (47.3 %) were deceased at last follow-up. Of the 45 deaths, 32 (71.1 %) were attributed to the intercurrent infection.

In summary, opportunistic infections are commonly reported in VEXAS syndrome. Prophylaxis for such infections remains paramount but no clear consensus on recommendations exists, highlighting the need for prospective studies. Moreover, furthering our understanding of pathophysiology of VEXAS syndrome and impairment in both innate and humoral immunity may clarify its contribution to infections in addition to high background immunosuppressive therapies.

空泡化，E1酶，x -连锁，自身炎症，躯体（VEXAS）综合征是一种多系统疾病，需要慢性免疫抑制。机会性感染很常见；然而，没有明确的预防方案。对文献进行了系统的回顾。对6篇发表的123例患者进行了评估。86例有人口统计学资料的患者；多数为男性（85例，98.8%），中位年龄73岁。80例患者报告了UBA1突变状态：p.Met41Thr （n = 43, 53.8%）、p.Met41Val （n = 17, 21.3%）和p.Met41Leu （n = 12, 15.0%）最为常见。在这些患者中，48例（60%）有潜在的骨髓增生异常综合征。许多患者多次住院治疗。报告感染病例如下：covid - 19 （n = 20）、吉罗氏肺囊虫肺炎（n = 16）、非结核分枝杆菌（NTM）（n = 16）、肠杆菌科（n = 14）、军团菌（n = 13）、水痘带状疱疹病毒（n = 11）和单纯疱疹病毒（n = 8）感染。每日强的松龙剂量等于或大于10mg，总体中位长期类固醇治疗持续时间为3.1年。值得注意的是，对于NTM，泼尼松龙的中位每日剂量为12.5 mg。强的松龙治疗PJP的中位剂量仅在一篇出版物中报道，包括6名患者，每天17毫克。在可获得数据的地方，95例患者中有45例（47.3%）在最后随访时死亡。在45例死亡中，32例（71.1%）是由于并发感染。总之，机会性感染通常在VEXAS综合征中报道。预防此类感染仍然是最重要的，但在建议上没有明确的共识，这突出了前瞻性研究的必要性。此外，进一步了解VEXAS综合征的病理生理学和先天免疫和体液免疫的损害可能会澄清它在高背景免疫抑制治疗之外对感染的贡献。

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引用次数: 0

Allogeneic hematopoietic stem cell transplantation in 18 patients with atypical inherited bone marrow failure syndromes: Efficacy and long-term outcomes 异基因造血干细胞移植治疗18例非典型遗传性骨髓衰竭综合征的疗效和长期预后

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-05-21 DOI: 10.1016/j.retram.2025.103519

Yimin Wang, Jing Wang, Qianqian Xiao, Xiaolin Yu, Xiaochen Song, Wenjun Li, Lei Deng, Yixi Hou, Fang Zhou

引用次数: 0

Anthracycline and arsenic trioxide-based regimens for the treatment of acute promyelocytic leukemia: thiamine levels monitoring importance 蒽环类药物和三氧化二砷治疗急性早幼粒细胞白血病：硫胺素水平监测的重要性

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-05-19 DOI: 10.1016/j.retram.2025.103520

Reda Garidi, Hassina Aftisse, Djedjiga Si Tayeb, Chahrazad Benchchouk, Nadia Sari Hassoun, Assia Alem, Tamim Alsuliman

引用次数: 0

Cytomegalovirus HLA antigen load as a new potential predictive factor after haploidentical stem cell transplantation 巨细胞病毒HLA抗原载量作为单倍体干细胞移植后新的潜在预测因子

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-05-14 DOI: 10.1016/j.retram.2025.103518

Antonio Milano , Jacopo Mariotti , Pietro Crivello , Giulia Di Maggio , Giorgia Cornacchini , Giuliana Lando , Silvano Rossini , Marialuisa Lavitrano , Stefania Bramanti , Roberto Crocchiolo

Among the complications occurring after allogeneic hematopoietic stem cell transplantation (HSCT), infection by human Cytomegalovirus (CMV) represents one of the most relevant in terms of morbidity/mortality and specific management is required by either monitoring viral load and administer anti-CMV therapies. Due to the physiological role of the Human Leucocyte Antigen (HLA) system in presenting foreign antigens to the adaptive immune system to enhance viral clearance, we measured here the HLA antigen load for two immunodominant CMV peptides and correlate with transplant outcome in 238 consecutive adult patients undergoing haploidentical HSCT at a single center.

Interestingly, a higher class I antigen load (i.e. above the median) for protein IE1 correlated with an inferior absolute incidence of CMV infection; moreover, a statistically significant correlation with lower non-relapse mortality and higher overall survival was observed (HR: 0.32, 0.12–0.84, p = 0.02; 0.34 (0.17–0.69, p = 0.003; respectively), with a protective effect in patients with high antigen load values.

Despite additional research is needed, our exploratory data support the role of the HLA polymorphism on CMV infection and survival after HSCT. The introduction of CMV antigen load as a new potential predictive factor might contribute to further define the post-transplant risk on an individualised basis.

在同种异体造血干细胞移植（HSCT）后发生的并发症中，人巨细胞病毒（CMV）感染是发病率/死亡率最相关的并发症之一，需要通过监测病毒载量和给予抗巨细胞病毒治疗来进行特异性管理。由于人类白细胞抗原（HLA）系统在将外来抗原呈递到适应性免疫系统以增强病毒清除方面的生理作用，我们在此测量了两种免疫优势CMV肽的HLA抗原负荷，并在单个中心测量了238例连续接受单倍体同种HSCT的成人患者的移植结果。有趣的是，IE1蛋白较高的I类抗原载量（即高于中位数）与CMV感染的绝对发生率较低相关；此外，与较低的非复发死亡率和较高的总生存率有统计学意义的相关性(HR: 0.32, 0.12-0.84, p = 0.02；0.34 (0.17-0.69, p = 0.003；)，对抗原负荷值高的患者有保护作用。尽管还需要进一步的研究，我们的探索性数据支持HLA多态性在巨细胞病毒感染和移植后生存中的作用。引入巨细胞病毒抗原负荷作为一个新的潜在预测因素可能有助于进一步确定个体化移植后风险。

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引用次数: 0

Multidimensional evaluation of CMV-specific T Cells: enhancing therapy through transcriptional insights cmv特异性T细胞的多维评估：通过转录的见解增强治疗

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-04-29 DOI: 10.1016/j.retram.2025.103517

Changchang Sun , Mingli Xu , Min Yan , Meiying Shen , Xiaojian Han , Hongbin Zhang , Chao Hu , Yingming Wang , Wang Wang , Aishun Jin , Yingying Wang

Adoptive immunotherapy with CMV-specific T cells (CMV-VSTs) has shown favorable efficacy and minimal adverse effects in clinical settings, serving as prophylaxis, preemptive and/or curative treatment for the restoration of CMV-specific immunity in patients after allogeneic hematopoietic stem cell transplantation. The establishment of a CMV-VST bank enables the prompt use of CMV-VSTs as off-the-shelf therapeutics. CMV-VSTs can be generated through cell culture or immunomagnetic selection based on IFN-γ secretion or multimer technology. In this study, we investigated the feasibility of generating CMV-VSTs via cell expansion after IFN-γ based immunomagnetic isolation, with the goal of establishing a good-quality, cost-effective local production approach. We also assessed the value of incorporating transcriptomic analysis into the current T cell evaluation framework. Our results demonstrate that good-quality CMV-VSTs can be produced using either autologous feeder cells or feeder cells from the rapid expansion protocol (REP), in combination with cytokines such as IL-2 or IL-7/IL-15. Phenotypic and functional analyses confirmed the consistent quality of the final T cell products and showed no significant differences across the various combinations of feeder cells and cytokines. However, transcriptomic analysis highlighted the advantages of using IL-7/IL-15 and autologous feeder cells. Collectively, our findings offer new insights into future strategies for the manufacturing of antigen-specific T cells and underscore the importance of comprehensive, multidimensional assessment in T cell-based immunotherapies.

cmv特异性T细胞（CMV-VSTs）过继免疫治疗在临床环境中显示出良好的疗效和最小的不良反应，可作为异基因造血干细胞移植后患者cmv特异性免疫恢复的预防、先发制人和/或治疗性治疗。CMV-VST库的建立使CMV-VST能够作为现成的治疗药物迅速使用。CMV-VSTs可以通过细胞培养或基于IFN-γ分泌或多重技术的免疫磁选择产生。在本研究中，我们研究了基于IFN-γ的免疫磁分离后通过细胞扩增产生CMV-VSTs的可行性，目的是建立一种高质量、高成本效益的本地生产方法。我们还评估了将转录组学分析纳入当前T细胞评估框架的价值。我们的研究结果表明，高质量的CMV-VSTs可以使用自体供体细胞或快速扩增方案（REP）的供体细胞，结合IL-2或IL-7/IL-15等细胞因子产生。表型和功能分析证实了最终T细胞产物的一致质量，并且在不同的饲养细胞和细胞因子组合中没有显着差异。然而，转录组学分析强调了使用IL-7/IL-15和自体饲养细胞的优势。总的来说，我们的发现为抗原特异性T细胞制造的未来策略提供了新的见解，并强调了在基于T细胞的免疫疗法中全面、多维评估的重要性。

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引用次数: 0