Experimental Hematology & Oncology最新文献

{"title":"Breakthroughs of CAR T-cell therapy in acute myeloid leukemia: updates from ASH 2024.","authors":"Haixiao Zhang, Hong-Hu Zhu","doi":"10.1186/s40164-025-00651-6","DOIUrl":"https://doi.org/10.1186/s40164-025-00651-6","url":null,"abstract":"<p><p>While chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for lymphoid malignancies, its greatest challenge remains in the treatment of acute myeloid leukemia (AML). Its success in AML has been limited by the ideal target antigen, myelosuppression, and immunosuppressive leukemia microenvironment. The 2024 ASH Meeting highlighted several cutting-edge advancements in AML-directed CAR T therapies, including clinical trials targeting CD33, CD123, CLL1, CD19, and IL1RAP, as well as novel engineering strategies such as dual-targeting CARs, inhibitory CAR designs, and genome-editing approaches to enhance safety and efficacy. Here, we summarize key findings from both clinical and preclinical studies, offering insights into the evolving landscape of CAR T-cell therapy for AML.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"57"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a microRNA profile in urine liquid biopsy with diagnostic and stratification value for bladder cancer classification, available through the open app BladdermiRaCan.","authors":"Julia Oto, Raquel Herranz, Emma Plana, Javier Pérez-Ardavín, David Hervás, Fernando Cana, Patricia Verger, David Ramos-Soler, Manuel Martínez-Sarmiento, César D Vera-Donoso, Pilar Medina","doi":"10.1186/s40164-025-00649-0","DOIUrl":"https://doi.org/10.1186/s40164-025-00649-0","url":null,"abstract":"<p><p>We aimed to identify a profile of urine microRNAs (miRNAs) with diagnostic and stratification potential in the whole range of bladder cancer (BC) categories, to avoid current invasive, harmful and expensive procedures. We collected a first morning urine sample from the screening (35 BC patients and 15 age- and gender-matched controls) and validation cohorts (172 BC and 94 controls). In the screening stage we analyzed the expression level of 179 miRNAs by real-time reverse transcription quantitative PCR in urine supernatants. miRNA levels in each sample were normalized by the levels of the previously identified and stably expressed miR-29c-3p. We performed an ordinal regression for each miRNA with False Discovery Rate (FDR) adjustment to identify dysregulated miRNAs, and an ordinal elastic net logistic regression model to identify a miRNA profile for BC diagnosis and stratification with the software R (v3.5.1). Next, we validated the most dysregulated miRNAs, and empirically identified the real miRNA targets in BC cells by miR-eCLIP immunoprecipitation and sequencing. We identified 70 dysregulated miRNAs in BC patients (p < 0.05 FDR-adjusted). With the expression level of 7 miRNAs in urine (miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p, miR-21-5p) we could stratify BC patients and control subjects. To enable the global use of our model, we developed the free BladdermiRaCan online tool. Furthermore, we identified miR-21-5p, miR-425-5p and miR-99a-5p as follow-up markers for BC relapse, and miR-21-5p and miR-221-3p as markers for metastasis. These miRNAs were also dysregulated in BC tissue sections from a subgroup of patients from which urine samples were studied. In conclusion, we have validated and patented a 7-miRNAs urine profile able to diagnose and stratify BC patients; BladdermiRaCan will enable the global use of our model. The experimentally verified target proteins identified for these miRNAs may unravel novel therapeutic targets.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"58"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.","authors":"HyunJun Kang, Melissa Valerio, Jia Feng, Long Gu, Dinh Hoa Hoang, Amanda Blackmon, Shawn Sharkas, Khyatiben Pathak, Jennifer Jossart, Zhuo Li, Hongyu Zhang, Bin Zhang, Patrick Pirrotte, J Jefferson P Perry, Robert J Hickey, Linda Malkas, Guido Marcucci, Le Xuan Truong Nguyen","doi":"10.1186/s40164-025-00650-7","DOIUrl":"https://doi.org/10.1186/s40164-025-00650-7","url":null,"abstract":"","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"56"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in chronic lymphocytic leukemia: advances and challenges.","authors":"Pan Gao, Yang Zhang, Jun Ma, Ya Zhang","doi":"10.1186/s40164-025-00644-5","DOIUrl":"https://doi.org/10.1186/s40164-025-00644-5","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treatment modalities and offering substantial benefits to patient outcomes. This review endeavors to synthesize and scrutinize the efficacy, merits, and limitations of the current immunotherapeutic strategies for CLL. The aim is to inform the selection of optimal treatment regimens tailored to individual patient needs. Furthermore, the review juxtaposes various therapeutic combinations to elucidate the comparative advantages of each approach, with the ultimate objective of enhancing patient prognosis and quality of life.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"53"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.","authors":"Meiling Zhang, Bin Zhang","doi":"10.1186/s40164-025-00647-2","DOIUrl":"https://doi.org/10.1186/s40164-025-00647-2","url":null,"abstract":"<p><p>Tumor microenvironment (TME) is a complex ecosystem composed of both cellular and non-cellular components that surround tumor tissue. The extracellular matrix (ECM) is a key component of the TME, performing multiple essential functions by providing mechanical support, shaping the TME, regulating metabolism and signaling, and modulating immune responses, all of which profoundly influence cell behavior. The quantity and cross-linking status of stromal components are primary determinants of tissue stiffness. During tumor development, ECM stiffness not only serves as a barrier to hinder drug delivery but also promotes cancer progression by inducing mechanical stimulation that activates cell membrane receptors and mechanical sensors. Thus, a comprehensive understanding of how ECM stiffness regulates tumor progression is crucial for identifying potential therapeutic targets for cancer. This review examines the effects of ECM stiffness on tumor progression, encompassing proliferation, migration, metastasis, drug resistance, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, stemness, metabolic reprogramming, and genomic stability. Finally, we explore therapeutic strategies that target ECM stiffness and their implications for tumor progression.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"54"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLS2 inhibition synergizes with copper to reprogram TCA cycle for cuproptosis-driven radiosensitization in esophageal cancer.","authors":"Wang Jing, Wenhao Wang, Yi Ding, Renya Zeng, Hui Zhu, Zhichao Kang, Alei Feng, Zhe Yang","doi":"10.1186/s40164-025-00653-4","DOIUrl":"https://doi.org/10.1186/s40164-025-00653-4","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is notorious for its poor prognosis. In the present study, the role of glutaminase 2 (GLS2) and copper (Cu) in the radiosensitivity of ESCC was explored. Both in vitro and in vivo experiments were conducted, and the results demonstrated that the knockdown of GLS2 could suppress cell proliferation and augment the sensitivity to radiotherapy (RT). The addition of Cu influenced cell viability and radiosensitivity. Notably, under normal GLS2 expression status, exogenous Cu augmented RT sensitivity without triggering cuproptosis. Mechanistically, the suppression of GLS2 interacted with Cu to downregulate lipoic acid synthase and dihydrolipoamide S-succinyltransferase, resulting in the reduction of the activity of α-ketoglutarate dehydrogenase complex and the obstruction of the tricarboxylic acid cycle, ultimately leading to the enhancement of RT sensitivity. These findings emphasize the significance of cuproptosis in ESCC radiotherapy and provide potential directions for therapeutic strategies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"55"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKG2D/CD28 chimeric receptor boosts cytotoxicity and durability of CAR-T cells for solid and hematological tumors.","authors":"Xia Teng, Shance Li, Chaoting Zhang, Huirong Ding, Zhihua Tian, Yuge Zhu, Ting Liu, Guanyu Zhang, Kang Sun, Huimin Xie, Jiaxin Tu, Zheming Lu","doi":"10.1186/s40164-025-00646-3","DOIUrl":"10.1186/s40164-025-00646-3","url":null,"abstract":"<p><strong>Background: </strong>CAR-T cell therapy faces challenges in solid tumor treatment and hematologic malignancy relapse, among which the limited persistence of CAR-T cells and target antigen downregulation are prominent factors. Therefore, we engineered an NKG2D/CD28 chimeric co-stimulatory receptor (CCR), leveraging its broad ligand expression on tumors to enhance the antitumor activity of MSLN CAR and CD19 CAR-T cells.</p><p><strong>Methods: </strong>We generated MSLN CAR-T and CD19 CAR-T cells co-expressing the NKG2D/CD28 CCR and assessed their antitumor efficacy in vitro and in vivo. CAR-T cell activation, differentiation, and exhaustion were analyzed over time following tumor antigen stimulation. Furthermore, a chronic antigen stimulation model was established using tumor cells with low antigen density to simulate the sustained antigenic pressure encountered in vivo treatment conditions.</p><p><strong>Results: </strong>Our study shows that NKG2D/CD28&CAR-T cells exhibit enhanced cytotoxicity against tumor cells, especially those with low antigen density, both in vitro and in vivo. Compared to conventional second-generation MSLN CAR or CD19 CAR-T cells, these dual-targeted NKG2D/CD28&CAR-T cells demonstrate superior sensitivity in recognizing and lysing low-density antigen-expressing lung cancer and leukemia cells, and they are capable of eradicating tumors with low-density antigen expression in vivo. Furthermore, the complementary co-stimulation provided by the 4-1BB and CD28 intracellular domains in the CAR and NKG2D/CD28 promotes cytokine secretion, reduces CAR-T cell exhaustion, and enhances the in vivo persistence of CAR-T cells, significantly improving their antitumor efficacy.</p><p><strong>Conclusion: </strong>The combination of CAR and NKG2D/CD28 offers a potent strategy to enhance the cytotoxicity and durability of CAR-T cells. This approach is promising for improving therapeutic outcomes in solid and hematological tumors and preventing recurrence in tumors with low target antigen density.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"52"},"PeriodicalIF":9.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Targeting and cytotoxicity of chimeric antigen receptor T cells grafted with PD1 extramembrane domain.","authors":"Ang Zhang, Shenyu Wang, Yao Sun, Yikun Zhang, Long Zhao, Yang Yang, Yijian Zhang, Lei Xu, Yangyang Lei, Jie Du, Hu Chen, Lian Duan, Mingyi He, Lintao Shi, Lei Liu, Quanjun Wang, Liangding Hu, Bin Zhang","doi":"10.1186/s40164-025-00645-4","DOIUrl":"10.1186/s40164-025-00645-4","url":null,"abstract":"","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"50"},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways.","authors":"Bailin He, Hong Chen, Jiaxu Wu, Shiqiu Qiu, Qiusui Mai, Qing Zeng, Cong Wang, Shikai Deng, Zihong Cai, Xiaoli Liu, Li Xuan, Chengyao Li, Hongsheng Zhou, Qifa Liu, Na Xu","doi":"10.1186/s40164-025-00639-2","DOIUrl":"10.1186/s40164-025-00639-2","url":null,"abstract":"<p><strong>Background: </strong>NK cells engineered to express interleukin-15 (IL-15) and a CD19-targeted chimeric antigen receptor (CAR) have been used to treat patients with relapsed and/or refractory B cell malignances, demonstrating encouraging outcomes and favorable safety profile. However, the effect of IL-21 in CAR-NK cell therapy remains unknown.</p><p><strong>Methods: </strong>CD19-specific CAR with 4-1BB costimulatory domain and cytokine IL-21 or IL-15 was constructed and transduced into peripheral blood (PB)-derived NK cells to produce CD19-CAR-IL21 NK cells (CAR-21) or CD19-CAR-IL15 NK cells (CAR-15), respectively. The phenotypic profile, transcriptomic characteristics, functionality and anti-tumor activity of CAR-21 NK cells and CAR-15 NK cells were compared.</p><p><strong>Results: </strong>Compared with CAR-NK cells co-expressing IL-15, CAR-NK cells co-expressing IL-21 exhibited significantly increased IFN-γ, TNF-α and Granzyme B production, as well as degranulation, in response to CD19⁺ Raji lymphoma cells, resulting in enhanced cytotoxic activity upon repetitive tumor stimulation. Furthermore, IL-21 co-expression improved the in vivo persistence of CAR-NK cells and significantly suppressed tumor growth in a xenograft Raji lymphoma murine model, leading to prolonged survival of CD19⁺ tumor-bearing mice. RNA sequencing revealed that CAR-21 NK cells have a distinct transcriptomic signature characterized by enriched in cytokine, cytotoxicity, and metabolic related signaling, when compared with CAR-15 NK or CAR NK cells.</p><p><strong>Conclusions: </strong>This study demonstrated that CD19-specific CAR-NK cells engineered to express IL-21 exhibit superior persistence and anti-tumor activity against CD19⁺ tumor compared to CAR-NK cells co-expressing IL-15, which might be a promising therapeutic strategy for treating patients with relapse or refractory B cell malignances.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"51"},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siltuximab for the treatment of early complications after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia in children, adolescents, and young adults.","authors":"Víctor Galán-Gómez, Berta González-Martínez, Anna Alonso-Saladrigues, Susana Rives, Blanca Herrero, Mi Kwon, Jose Sánchez-Pina, Jordi Minguillón, Isabel Martínez-Romera, Isabel Mirones Aguilar, Carmen Mestre-Durán, Gema Casado, María Sánchez-Martín, Carlos Echecopar, Carlos González-Pérez, Odelaisy León-Triana, Cristina Aguirre-Portolés, Águeda Molinos-Quintana, Pere Barba, Pascual Balsalobre, Antonio Pérez-Martínez","doi":"10.1186/s40164-025-00638-3","DOIUrl":"10.1186/s40164-025-00638-3","url":null,"abstract":"<p><strong>Background: </strong>Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are complications associated with CAR T-cell therapy. Siltuximab directly binds interleukin-6 (IL-6) and may be safe and effective as first-line therapy for CRS or ICANS.</p><p><strong>Methods: </strong>A retrospective study was conducted on pediatric, adolescent and young adult (AYA) patients treated with siltuximab after CAR T-cell therapy for B-ALL.</p><p><strong>Results: </strong>A total of 118 patients treated were included: 97 patients developed CRS (82%), and 26 patients (22%) developed ICANS. Sixty-five of those that developed CRS (55%), received treatment. In 46/65 (71%), tocilizumab was administered as anti-IL-6 drug, and 19/65 (29%) patients received siltuximab to treat tocilizumab-refractory CRS (n = 13, 68%), or as first-line CRS treatment (n = 6, 32%). Nine patients treated with siltuximab (47%) developed ICANS. With a median follow-up of 12.1 months, 7 patients remained alive.</p><p><strong>Conclusions: </strong>To the best of our knowledge, we present the largest reported cohort of patients treated with siltuximab for CRS following CAR T-cell therapy for B-ALL. Siltuximab's safety profile and its inhibition of IL-6 effects suggest that it should be investigated as first-line therapy in prospective clinical trials.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"49"},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}