Biomolecules & Therapeutics最新文献_第8页

Immunosenescence in Human Disease: Mechanistic Insights and Therapeutic Opportunities. 人类疾病中的免疫衰老：机制见解和治疗机会。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.222

Young-In Kim, Seo-Hee Oh, Tae Kyoung Lim, Heewon Lee, Sebin Lee, Sun-Young Chang

{"title":"Immunosenescence in Human Disease: Mechanistic Insights and Therapeutic Opportunities.","authors":"Young-In Kim, Seo-Hee Oh, Tae Kyoung Lim, Heewon Lee, Sebin Lee, Sun-Young Chang","doi":"10.4062/biomolther.2025.222","DOIUrl":"10.4062/biomolther.2025.222","url":null,"abstract":"Immunosenescence, an age-associated decline in immune function, is increasingly recognized as a central determinant of health and disease in older adults. Characterized by thymic involution, loss of naïve T cells, contraction of T cell receptor diversity, accumulation of senescent and exhausted lymphocytes, and a chronic inflammatory state known as inflammaging, immunosenescence compromises both innate and adaptive immune responses. Immunosenescence contributes to the pathogenesis of diverse age-related diseases. In autoimmune and metabolic diseases, premature accumulation of senescent T cells and impaired regulatory T cell function drive chronic inflammation and tissue damage, while in neurodegenerative diseases, microglial aging and sustained neuroinflammation exacerbate neuronal loss. These findings highlight immunosenescence as a unifying mechanism linking aging to systemic and organ-specific pathologies. Advances in biomarker discovery, including phenotypic markers, telomere attrition, and epigenetic signatures, have enabled the quantitative assessment of immune aging, while emerging therapeutic strategies, such as cytokine modulation, mTOR inhibition, senolytics, and epigenetic reprogramming, show promise in restoring immune competence. Here, we summarize recent research on immunosenescence in various diseases, particularly chronic inflammatory, metabolic, and neurodegenerative diseases, and suggest novel strategies for the development of senolytic drugs.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"238-248"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with CDK4-Amplification. 利用cdk4扩增技术鉴定复杂核型软组织肉瘤候选生物标志物的生物信息学分析。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.157

Eun-Young Lee, Hyun Sang Cho, June Hyuk Kim, Hyun Guy Kang, Jong Woong Park, Ahyoung Cho, Hye Jin You

{"title":"Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with CDK4-Amplification.","authors":"Eun-Young Lee, Hyun Sang Cho, June Hyuk Kim, Hyun Guy Kang, Jong Woong Park, Ahyoung Cho, Hye Jin You","doi":"10.4062/biomolther.2025.157","DOIUrl":"10.4062/biomolther.2025.157","url":null,"abstract":"Soft tissue sarcomas (STSs), a diverse group of mesenchymal malignancies, are characterized primarily by copy-number alterations rather than a high tumor mutation burden. In this study, we sought to identify expression-based biomarkers in complex karyotype STS (CKS) with CDK4-amplification to support improved therapeutic strategies. Using transcriptome data from National Cancer Center (NCC)-CKS samples, we selected genes whose expression levels were more than two-fold higher or less than half in tumor tissues compared with normal tissues. These genes were further filtered by CDK4-amplification status, resulting in 30 candidates, which were refined to 14 differentially expressed genes (DEGs) based on false discovery rate (FDR) significance. Bioinformatics analyses revealed enriched pathways and gene-gene networks related to redox regulation and growth-factor-driven signal transduction, indicating metabolic alterations that may promote tumor survival in CDK4-amplified CKS. A subset of the 14 genes demonstrated prognostic significance in CDK4-amplified patients from the TCGA cohort. Additionally, immune cell marker analysis showed associations between CDK4-amplification and innate immune cell signatures. Together, our findings identify promising therapeutic and prognostic targets linked to CDK4-amplification in CKS. These biomarkers warrant further investigation and may ultimately contribute to improved clinical outcomes for patients with CKS.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"379-390"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skin Organoids in Proteostasis Research: Early Insights into Aging. 皮肤类器官在蛋白质平衡研究：对衰老的早期洞察。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.268

Muhammad Kamal Hossain, Hyung-Ryong Kim

{"title":"Skin Organoids in Proteostasis Research: Early Insights into Aging.","authors":"Muhammad Kamal Hossain, Hyung-Ryong Kim","doi":"10.4062/biomolther.2025.268","DOIUrl":"10.4062/biomolther.2025.268","url":null,"abstract":"The decline of proteostasis is a central hallmark of aging, the earliest manifestations of which have remained difficult to capture in human tissues with conventional model systems. The skin is a continuously renewing and environmentally exposed organ offering a uniquely accessible window into aging biology. Skin organoid technologies allow for long-term culturing of human epidermal and full-thickness skin-like tissues that accurately recapitulate important aspects of cellular heterogeneity, spatial organization, and stem cell dynamics. In this perspective, we discuss how skin organoids are beginning to reveal early proteostasis alterations-encompassing impaired protein folding, reduced proteasomal activity, and autophagy dysfunction-that precede overt structural and functional hallmarks of skin aging, with particular emphasis on underexplored regulators- sebaceous gland and sebocyte-specific proteostasis, autophagy, and inflammaging. We also highlight emerging insights, conceptual challenges, and experimental limitations, and outline future directions for integrating skin organoids with skin-on-a-chip, single-cell proteomics, and stress-reporting approaches to advance proteostasis-targeted interventions in skin aging.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"264-278"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clemastine Restores Myelination Protein Expression in S16 Schwann Cells by Enhancing AMPK Activation and Reducing H₂O₂-Induced Oxidative Stress. Clemastine通过增强AMPK激活和减少h2o2诱导的氧化应激，恢复S16雪旺细胞的髓鞘蛋白表达。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.188

Chawon Yun, So Young Lee, Jun Hong Won, Ga Hee Kim, Tae Hyun Kim, Jung Il Lee

{"title":"Clemastine Restores Myelination Protein Expression in S16 Schwann Cells by Enhancing AMPK Activation and Reducing H2O2-Induced Oxidative Stress.","authors":"Chawon Yun, So Young Lee, Jun Hong Won, Ga Hee Kim, Tae Hyun Kim, Jung Il Lee","doi":"10.4062/biomolther.2025.188","DOIUrl":"10.4062/biomolther.2025.188","url":null,"abstract":"Peripheral nerve injury and oxidative stress can severely impair Schwann cell function by disrupting the expression of key myelin proteins, promoting intracellular lipid accumulation, and damaging mitochondrial integrity. These pathological changes are central to various neurodegenerative disorders and chemotherapy-induced peripheral neuropathy, yet effective therapeutic approaches remain limited. Clemastine, an FDA-approved antihistamine with known remyelination-enhancing effects in the central nervous system, has not been thoroughly explored for its protective role in peripheral myelinating cells under oxidative stress. In this study, we investigated the time-dependent protective effects of Clemastine in S16 Schwann cells exposed to hydrogen peroxide (H2O2) as a model of oxidative injury. Treatment with Clemastine significantly increased the expression of myelin-related proteins such as myelin protein zero (MPZ), alongside in increase in AMPK phosphorylation at Thr172. However, co-treatment with H2O2 ensued oxidative damage, leading to reduced pAMPK(T172) and MPZ expression, elevated ROS levels, and increased lipid accumulation. These results suggest that oxidative stress can attenuate Clemastine's effects in association with disrupted redox balance and energy metabolism. Subsequent treatment with Metformin (Met), a pharmacological activator of AMPK, was associated with partial recovery from H2O2-induced oxidative damage. Overall, our findings support the potential of a combinatorial approach using Clemastine and Met to promote myelin-related protein expression and lipid metabolic balance in Schwann cells under oxidative stress, rather than establishing a definitive synergistic or causal mechanism.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"345-355"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hemostasis-Sparing Antiplatelet Therapy: Current Concepts and Emerging Targets in Arterial Thrombosis. 保留止血的抗血小板治疗：动脉血栓形成的最新概念和新靶点。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.214

Ji Won Park, Eun Bee Oh, Tong-Shin Chang

{"title":"Hemostasis-Sparing Antiplatelet Therapy: Current Concepts and Emerging Targets in Arterial Thrombosis.","authors":"Ji Won Park, Eun Bee Oh, Tong-Shin Chang","doi":"10.4062/biomolther.2025.214","DOIUrl":"10.4062/biomolther.2025.214","url":null,"abstract":"Arterial thrombosis remains a leading cause of cardiovascular morbidity and mortality despite widespread use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors. Although these agents reduce ischemic events, their efficacy is counterbalanced by dose-dependent bleeding and their inability to distinguish pathological platelet activation from physiological hemostasis. Recent advances in platelet biology have shifted therapeutic development toward hemostasis-sparing antiplatelet strategies- approaches designed to selectively inhibit thrombosis while preserving baseline hemostatic function. These strategies target upstream adhesion receptors (GPVI, GPIb-vWF, CLEC-2) and receptor-proximal intracellular signaling nodes (SYK, BTK, PI3Kβ, PLCγ2, NADPH oxidases) that are preferentially engaged under high-shear or strongly prothrombotic conditions. Early-phase clinical and translational studies of such agents demonstrate antithrombotic efficacy with minimal impact on bleeding time, supporting their mechanistic selectivity. In parallel, contemporary clinical practice increasingly utilizes individualized risk assessment, platelet function testing, and genetic profiling to tailor treatment intensity. This integration of mechanism-selective agents with patient-specific risk evaluation forms the basis of precision-based thrombosis prevention, a framework aimed at aligning the duration and depth of platelet inhibition with the dynamic balance between ischemic and bleeding risk. Together, these developments mark a paradigm shift from broad platelet suppression toward rational, context-adaptive, and safer antiplatelet therapy.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"225-237"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanisms Underlying the Anti-Cancer Effects of Tangeretin, a Phytochemical from Citrus Extracts. 柑橘提取物中的植物化学物质橘皮素抗癌作用的分子机制

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-03-01 DOI: 10.4062/biomolther.2025.141

Seung-Hyeon Ahn, Kyung-Chul Choi

{"title":"Molecular Mechanisms Underlying the Anti-Cancer Effects of Tangeretin, a Phytochemical from Citrus Extracts.","authors":"Seung-Hyeon Ahn, Kyung-Chul Choi","doi":"10.4062/biomolther.2025.141","DOIUrl":"10.4062/biomolther.2025.141","url":null,"abstract":"Cancer is one of the diseases with high incidence and mortality rates. As a result, many studies have led to the development of therapeutic agents such as immune checkpoint inhibitors. However, the research on cancer treatment is still essential because of problems including drug resistance, genetic variation among patients, and drug toxicity. To address these problems, several candidate chemicals, including phytochemicals, have been studied for cancer treatment. Phytochemicals exhibit a variety of biochemical and physiological functions in the body and have been studied as having lower toxicity than synthetic chemicals. These properties have led to research into their potential as anti-cancer agents as well as their therapeutic applications for a variety of other diseases. The structural diversity of phytochemicals leads to considerable variations in their mechanisms of action. Therefore, it is important to understand the mechanism of action of each phytochemical when studying phytochemicals. Tangeretin (TAN) is mainly extracted from citrus fruits and is characterized by the presence of a methyl group. The presence of a methyl group in TAN is thought to enhance its intracellular uptake and confer greater resistance to degradation compared with other phytochemicals. Previous studies on the use of TAN in cancer treatment have mainly focused on its ability to induce oxidative stress as the primary anti-cancer mechanism. In addition, some studies suggest that TAN also exerts various other anti-cancer effects, such as upregulating tumor suppressor proteins, inducing apoptosis, and reducing the proportion of cancer stem cells (CSCs). This review highlights the anti-cancer effects of TAN in different cancers and aims to provide data to support future research.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"279-290"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lycium Radicis Cortex and Its Kukoamine Constituents Attenuate Sarcopenia by Modulating Anabolic and Catabolic Pathways. 枸杞皮及其苦莨菪碱成分通过调节合成代谢和分解代谢途径减轻肌肉减少症。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-12-02 DOI: 10.4062/biomolther.2025.134

Jae-Yong Kim, Rak Ho Son, Sang-Yoon Kim, Ji Hoon Kim, Sunhoo Kim, Chul Young Kim

{"title":"Lycium Radicis Cortex and Its Kukoamine Constituents Attenuate Sarcopenia by Modulating Anabolic and Catabolic Pathways.","authors":"Jae-Yong Kim, Rak Ho Son, Sang-Yoon Kim, Ji Hoon Kim, Sunhoo Kim, Chul Young Kim","doi":"10.4062/biomolther.2025.134","DOIUrl":"10.4062/biomolther.2025.134","url":null,"abstract":"Lycium Radicis Cortex (LRC), derived from the root bark of Lycium chinense Mill., has traditionally been used in East Asian medicine to mitigate heat in the blood and consumptive fever. This study investigates LRC's effects on skeletal muscle in aged mice subjected to forced exercise and examines the protective properties of its primary constituents, kukoamines A (KA) and B (KB), against dexamethasone (DEX)-induced muscle atrophy. Sixteen-month-old male C57BL/6 mice underwent regular swimming and received oral LRC supplementation for 8 weeks. The effects of KA and KB on muscle atrophy were further explored using C2C12 myotubes treated with DEX. LRC administration significantly enhanced muscle mass, strength, and endurance, while reducing plasma lactate and creatinine levels compared to the control group. LRC also upregulated mRNA expression of MyoD, myogenin, MHC, Akt, and mTOR, and downregulated myostatin, FoxO3a, MuRF1, and atrogin-1 in gastrocnemius and soleus muscles. Furthermore, KA and KB alleviated DEX-induced muscle atrophy in C2C12 myotubes by reducing proteolysis and ROS production, enhancing SOD activity, and improving mitochondrial function. Taken together, LRC may be a useful supplement in exercise-based muscle strengthening and amelioration of muscle disorders, and KA and KB have shown potential as preventive and therapeutic agents for muscle atrophy, indirectly suggesting that the efficacy of LRC is attributed to KA and KB.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"189-201"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gapmer Antisense Oligonucleotide Targeting E-Cadherin Rescues Abnormal Keratinization in X-Linked Ichthyosis Models. 靶向e -钙粘蛋白的Gapmer反义寡核苷酸可拯救x连锁鱼鳞病模型中的异常角化。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-12-22 DOI: 10.4062/biomolther.2025.228

Ji Heung Kwak, Tae-Uk Kwon, Yeo-Jung Kwon, Hyemin Park, Yoon-Ji Kang, Jeongeun Shin, Young-Jin Chun

{"title":"Gapmer Antisense Oligonucleotide Targeting E-Cadherin Rescues Abnormal Keratinization in X-Linked Ichthyosis Models.","authors":"Ji Heung Kwak, Tae-Uk Kwon, Yeo-Jung Kwon, Hyemin Park, Yoon-Ji Kang, Jeongeun Shin, Young-Jin Chun","doi":"10.4062/biomolther.2025.228","DOIUrl":"10.4062/biomolther.2025.228","url":null,"abstract":"X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of E-cadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led to downregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2'-O-methoxyethyl and phosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin-targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"213-224"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Cancer Immunotherapy: Chimeric Antigen Receptor (CAR)-T Cell Engineering through Novel Screening Methods. 推进癌症免疫治疗：嵌合抗原受体(CAR)-T细胞工程通过新的筛选方法。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-12-31 DOI: 10.4062/biomolther.2025.204

Junyoung Ha, Jihye Seong

{"title":"Advancing Cancer Immunotherapy: Chimeric Antigen Receptor (CAR)-T Cell Engineering through Novel Screening Methods.","authors":"Junyoung Ha, Jihye Seong","doi":"10.4062/biomolther.2025.204","DOIUrl":"10.4062/biomolther.2025.204","url":null,"abstract":"Cancer immunotherapy represents a paradigm-shifting achievement in oncology. Particularly, chimeric antigen receptor (CAR)-T cell therapy utilizing genetically engineered T cells has produced remarkable clinical responses in hematological malignancies. However, significant challenges still remain including limited efficacy in solid tumors and critical safety concerns. The functionality of CAR-T cells depends on their synthetic receptor, CAR, which redirects T cell specificity and enhances effector functions. Therefore, optimal CAR engineering is crucial for successful development of CAR-T cell therapy. In this review, we discuss the limitations of current CAR screening methods, which primarily assess antigen binding affinity in vitro and often fail to predict T cell function and in vivo therapeutic performance. Advanced cell-based screening platforms have been developed to overcome these limitations. We overview the principles of these CAR screening systems utilizing reporter cell lines. While most are based on the detection of antigen binding properties or CAR-T cell activation markers, we emphasize a FRET-based immunological synapse biosensor as a powerful system that directly assesses CAR activation upon antigen binding. This platform offers significant advantages in speed and scalability for predicting CAR-T cell functionality. We also discuss recent advances in CAR library screening directly in primary T cells, which provides more physiologically relevant data. Such advanced platforms are essential to accelerate the development of safe and effective CAR-T therapy for solid tumors, ultimately expanding the therapeutic potential of this transformative cancer treatment.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 1","pages":"30-44"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical Pharmacological and Toxicological Evaluation of SB5794, a Novel Aryl Hydrocarbon Receptor Modulator on the Kynurenine-AhR Axis. 新型芳基烃受体Kynurenine-AhR轴调节剂SB5794的临床前药理和毒理学评价

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-12-31 DOI: 10.4062/biomolther.2025.230

Daewon Cha, Soo-Jung Choi, Hyunwoo Park, Dae Young Lee, Min Sung Joo, Wonhyung Lee, Jungsang Park, Eunhye Lee, Hakwon Kim

{"title":"Preclinical Pharmacological and Toxicological Evaluation of SB5794, a Novel Aryl Hydrocarbon Receptor Modulator on the Kynurenine-AhR Axis.","authors":"Daewon Cha, Soo-Jung Choi, Hyunwoo Park, Dae Young Lee, Min Sung Joo, Wonhyung Lee, Jungsang Park, Eunhye Lee, Hakwon Kim","doi":"10.4062/biomolther.2025.230","DOIUrl":"10.4062/biomolther.2025.230","url":null,"abstract":"Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti-PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 1","pages":"146-153"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0