Experimental Hematology & Oncology最新文献

{"title":"Brain metastasis-associated cancer fibroblasts drive tumor progression and therapeutic resistance through IL26 and CX3CL1 signaling in non-small-cell lung cancer.","authors":"S M Abdus Salam, Eshrat Jahan, Eun-Jung Ahn, Sung Sun Kim, Yeong Jin Kim, Sue Jee Park, Tae-Young Jung, In-Young Kim, Shin Jung, Roo Ji Lee, Jae-Hyuk Lee, Joon Haeng Rhee, Kyung Keun Kim, Min-Hee Yi, Kyung-Hwa Lee, Kyung-Sub Moon","doi":"10.1186/s40164-025-00713-9","DOIUrl":"10.1186/s40164-025-00713-9","url":null,"abstract":"<p><p>Brain metastases (BM) from non-small cell lung cancer (NSCLC) represent a significant clinical challenge, characterized by poor prognosis and treatment resistance. While cancer-associated fibroblasts (CAFs) are recognized as crucial components of the BM tumor microenvironment (TME), their mechanistic contributions to disease progression and therapeutic resistance remain poorly understood. In this study, we demonstrated that patient-derived BM-CAFs significantly enhanced NSCLC cell proliferation, migration, invasion and therapeutic resistance in vitro. Mechanistically, BM-CAFs promoted epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) phenotypes through upregulation of key transcription factors. In-vivo experiments showed that co-injection of NSCLC cells with BM-CAFs accelerated tumor growth and enhanced cisplatin resistance. Molecular analysis revealed these effects were mediated through distinct mechanisms whereby IL26 activated the JAK-STAT3 pathway, while CX3CL1 activated both JAK-STAT3 and AKT-mTOR pathways. Importantly, neutralizing antibodies against IL26 and CX3CL1 effectively suppressed their respective signaling pathways and reversed EMT and CSC characteristics. In summary, our findings establish the IL26 and CX3CL1 signaling as a critical mediator of BM-CAF-induced tumor progression and therapy resistance in NSCLC BM, suggesting a potential therapeutic strategy for this challenging disease.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"120"},"PeriodicalIF":13.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198811","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":"Novel tumor-infiltrating lymphocytes therapy in solid tumors: latest updates from 2025 ASCO annual meeting.","authors":"Yanan Ma, Xuan Su, Huijing Feng","doi":"10.1186/s40164-025-00711-x","DOIUrl":"10.1186/s40164-025-00711-x","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocyte (TIL) therapy, a highly promising form of adoptive cell therapy (ACT), has demonstrated success in treating advanced melanoma. Notably, innovative TIL-based monotherapies and combination regimens have provided durable clinical responses and survival benefits for patients with various solid tumors. This article summarizes recent advances in TIL therapy for solid tumors presented at the 2025 ASCO Annual Meeting, highlighting monotherapies such as Lifileucel, LM103, OBX-115, GT101, GT300, GT201, and HS-IT101, as well as combination strategies with the oncolytic adenovirus TILT-123 or pembrolizumab.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"121"},"PeriodicalIF":13.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198768","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":"Revisiting thrombophilia testing: leveraging next-generation sequencing for precision in VTE management.","authors":"Ilham Youssry, Nardeen Ayad","doi":"10.1186/s40164-025-00698-5","DOIUrl":"10.1186/s40164-025-00698-5","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality, particularly among individuals with inherited thrombophilia. Despite the widespread use of thrombophilia testing, its clinical value is often questioned due to inconsistent guidelines and limited prospective evidence. Traditional testing panels target only a narrow set of common variants-such as Factor V Leiden and Prothrombin G20210A-and may miss rare, complex, or combined mutations, especially in high-risk patients, including pediatric populations and those with unprovoked events or atypical presentations. This correspondence aims to re-evaluate the clinical role of thrombophilia testing in light of next-generation sequencing (NGS), a technology that offers a broader, more precise assessment of heritable thrombotic risk. We discuss how NGS improves variant detection, enhances risk stratification, and supports a precision medicine framework-particularly in clinical scenarios where standard algorithms fail. By integrating emerging evidence and real-world applications, we advocate for an updated, individualized approach to genetic testing in VTE care.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"118"},"PeriodicalIF":13.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198874","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":"Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma.","authors":"Wenming Chen, Chengcheng Fu, Baijun Fang, Aibin Liang, Zhongjun Xia, Yanjuan He, Jin Lu, Hui Liu, Ming Hou, Zhen Cai, Wei Yang, Siguo Hao, Songfu Jiang, Hongmei Jing, Jing Liu, Xin Du, Rong Fu, Heng Mei, Zunmin Zhu, Yanli Yang, Hong Liu, Xingxing Meng, Nishanthan Rajakumaraswamy, Daijing Yuan, Huamao Wang, Zonghai Li","doi":"10.1186/s40164-025-00710-y","DOIUrl":"10.1186/s40164-025-00710-y","url":null,"abstract":"<p><strong>Background: </strong>Zevorcabtagene autoleucel (zevor-cel) is a fully human autologous CAR T-cell therapy targeting B-cell maturation antigen approved in China since 2024 for patients with relapsed/refractory multiple myeloma (RRMM).</p><p><strong>Methods: </strong>LUMMICAR STUDY 1 is a phase 2, single-arm study conducted across 23 centers in China. RRMM patients aged ≥ 18 to ≤ 75 years with measurable disease who had received ≥ 3 prior lines of therapy, with adequate organ function and bone marrow reserve, with an Eastern Cooperative Oncology Group (ECOG) score of 0-1, were eligible. Patients previously treated with any CAR T-cell therapy, or any BCMA-directed therapy were ineligible. The primary endpoint was objective response rate (ORR) determined by an Independent Review Committee. The secondary endpoints included ORR determined by investigator, additional efficacy outcomes including complete response (CR)/ stringent complete response (sCR) rate, duration of response (DOR), minimal residual disease negativity, safety outcomes including incidence and severity of adverse events, and pharmacokinetics of zevor-cel.</p><p><strong>Results: </strong>Overall, 125 patients underwent apheresis, 105 patients received lymphodepletion, 102 patients (median age of 59.5 [range: 38, 75] years; 53.9% male and 46.1% female) received zevor-cel. The ORR was 92.2% (95% CI 85.13-96.55) with 70 patients (68.6%) achieving sCR and 3 (2.9%) achieving CR. At a median follow-up of 20.3 (interquartile range [IQR] 12.5, 23.8) months, 45 (44.1%) progression-free survival (PFS) events and 20 (19.6%) overall survival (OS) events were observed, the DOR, PFS and OS data were not mature. Cytokine release syndrome was reported in 92 (90.2%) patients, with grade 3 or 4 events in 7 (6.9%) patients. Immune effector cell associated neurotoxicity syndrome was reported in 2 patients at grade 1; no zevor-cel-related grade ≥ 3 neurotoxicity occurred.</p><p><strong>Conclusion: </strong>Zevor-cel induces deep and durable responses in heavily pre-treated RRMM patients with a manageable safety profile.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"119"},"PeriodicalIF":13.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198892","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":"Precise regulation of RAS-Mediated PI3Kα activation: therapeutic potential of BBO-10203 in cancer treatment.","authors":"Ziyi Fan, Erqing Tan, Bin Song","doi":"10.1186/s40164-025-00706-8","DOIUrl":"10.1186/s40164-025-00706-8","url":null,"abstract":"<p><p>In recent years, the Phosphoinositide-3-Kinase α (PI3Kα) signaling pathway has been increasingly recognized as a critical driver of tumorigenesis, particularly in breast cancer drug resistance and other solid tumors. Although conventional PI3Kα inhibitors (e.g., Alpelisib) have shown efficacy in extending progression-free survival in patients with PI3Kα-mutant breast cancer, their clinical application remains constrained by off-target toxicities, particularly hyperglycemia, which limits dosing and therapeutic feasibility. Building on recent preclinical findings, this study introduces BBO-10203, a first-in-class, orally bioavailable small-molecule inhibitor targeting the RAS-PI3Kα interaction. The compound is rationally designed to selectively and covalently bind to Cysteine 242 (Cys242) within the Rat Sarcoma (RAS)-Binding Domain (RBD) of PI3Kα, thereby effectively disrupting RAS-mediated PI3Kα activation. This unique mechanism confers potent in vivo antitumor activity while preserving insulin-regulated glucose metabolism, thereby mitigating metabolic adverse effects.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"115"},"PeriodicalIF":13.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191552","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":"Tumor-priming CD8⁺ natural killer T-like cells as an efficient novel cell therapy for relapsed/refractory multiple myeloma.","authors":"Juheon Lee, Eunjeong Choi, Bohwa Han, Jeong-A Kim, Dana Jung, Kyeong-Hee Kim, Sung Yong Oh, Sung-Hyun Kim, Kyung-Soo Ha, Ji-Hoon Kim, Ji Hyun Lee, Duck Cho, Junsang Doh, Seok-Ho Kim","doi":"10.1186/s40164-025-00707-7","DOIUrl":"10.1186/s40164-025-00707-7","url":null,"abstract":"<p><strong>Background: </strong>Relapsed and refractory multiple myeloma (RRMM) remains a major clinical challenge, as most patients eventually relapse following standard treatments and are left with limited therapeutic options. Although b-cell maturation antigen (BCMA) CAR-T cell therapy has recently shown remarkable efficacy in select patients, broader implementation is hindered by its reliance on autologous cells, prolonged manufacturing timelines, high costs, and severe immune-related toxicities. These challenges have prompted an urgent demand for safer, more accessible, and rapidly applicable immunotherapeutic alternatives.</p><p><strong>Methods: </strong>CBMC (cord blood mononuclear cells) were cultured with irradiated BMMC (bone marrow mononuclear cells) from RRMM patients in the presence of defined cytokines, aiming to develop a new therapeutic immune cell product for RRMM. Their phenotypic and functional characteristics, including non-MHC-restricted and MHC-restricted cytotoxicity mechanisms, were analyzed using surface marker profiling, cytokine secretion assays, in vitro cytotoxicity assays, functional and blocking assays. Antitumor activity was evaluated in xenograft mouse models using MM.1 S and RPMI-8226 cells.</p><p><strong>Results: </strong>We successfully generated CD8⁺ NKT-like cells through tumor priming, which exhibited potent cytotoxicity and elevated cytokine production against multiple myeloma cell lines and primary RRMM samples. Mechanistically, tumor-priming CD8⁺ NKT-like cells (TPNC) cytotoxicity was mediated by both non-MHC-restricted pathways involving LFA-1 and DNAM-1, and MHC-restricted, TCR-mediated recognition. TPNC efficiently formed immune synapses, rapidly polarized cytotoxic granules, and engaged in serial killing. In xenograft models, TPNC significantly suppressed tumor progression, prolonged survival, and persisted in circulation without observable toxicity. Based on these findings, we extended the tumor-priming strategy to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), successfully generating TPNC with robust cytotoxic activity. In ALL samples, TPNC exhibited cytotoxicity comparable to anti-CD19 CAR-NK cells.</p><p><strong>Conclusions: </strong>TPNC represents a novel cytotoxic lymphocyte product generated through tumor-driven priming. Their dual recognition capacity, functional versatility, and favorable safety profile highlight their potential as a scalable and personalized immunotherapy platform for hematologic malignancies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"116"},"PeriodicalIF":13.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191532","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":"FGL1-mediated lymph node metastasis in stage T1 non-small cell lung cancer: therapeutic targeting.","authors":"Xi-Yang Tang, Run-Ze Zhang, Zhi-Bo Feng, Yu-Long Zhou, Wei-Guang Du, Chen Shu, Yang Shen, Meng-Chao Li, Jun-Chao Cai, Xiao-Long Yan, Nan Ma, Jin-Bo Zhao","doi":"10.1186/s40164-025-00709-5","DOIUrl":"10.1186/s40164-025-00709-5","url":null,"abstract":"<p><strong>Background: </strong>Approximately 30% of patients with stage T1 non-small cell lung cancer (NSCLC) have mediastinal (N2) lymph node metastasis; however, the underlying mechanism remains unclear.</p><p><strong>Methods: </strong>The cells likely mediating N2 lymph node metastasis in T1 NSCLC were identified by single-cell sequencing. The expression and function of the main functional gene high fibrinogen-like protein 1 (FGL1) in this cell subgroup were analyzed by single-cell analysis. Transcriptome sequencing, metabolome sequencing, and mass spectrometry combined with in vitro and in vivo experiments were conducted, and therapeutic validation was performed using shFGL1_AAV9 and shFGL1_AAV6.</p><p><strong>Results: </strong>A novel cell subgroup characterized by FGL1 expression was identified (CCNE1(+) cells). FGL1 expression coincided with the appearance of this cell subgroup, suggesting that FGL1 + cells mediate T1 NSCLC N2 lymph node metastasis. Mass spectrometry combined with transcription sequencing and metabonomics revealed that FGL1 may affect glycolysis regulators and participate in epithelial-to-mesenchymal transition in NSCLC via the PI3K/AKT/HIF-1α pathway. Further analyses suggested that FGL1 promotes tumor proliferation, metastasis, and lymph tube formation, ultimately inducing lymph node metastasis. This was verified in vivo and in vitro. FGL1 knockdown inhibited these processes. Finally, shFGL1_AAV9 and shFGL1_AAV6 were verified as novel targeted therapies to knock down FGL1 in vivo, supporting the identification of new therapeutic targets to inhibit NSCLC metastasis.</p><p><strong>Conclusion: </strong>We elucidated the role of FGL1 in NSCLC, proposing that FGL1 acts like a \"shield machine cutter\" in mediating T1 NSCLC N2 lymph node tube formation, creating metastasis channels. This provides the basis for novel FGL1-targeting treatment strategies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"117"},"PeriodicalIF":13.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191558","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":"Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.","authors":"Yuqian Wang, Cheng Jiang, Huiling Zhou, Rui Han","doi":"10.1186/s40164-025-00705-9","DOIUrl":"10.1186/s40164-025-00705-9","url":null,"abstract":"<p><p>This review introduces a paradigm-shifting concept of Dual Distinct Immunotherapy (DDI), which strategically integrates two distinct immunotherapeutic modalities to overcome the limitations of current monotherapies and dual immune checkpoint inhibitor (ICI) combinations. The concept of DDI extends beyond traditional ICI combinations to encompass various innovative pairings: ICIs with oncolytic viruses (OVs), adoptive cell therapies (CAR-T/TIL), cancer vaccines, or cytokine therapies. These combinations demonstrate unique synergistic mechanisms and enhanced therapeutic potential through multi-faceted immune activation. Significantly, this work advances the field by analyzing potential third-agent sensitizers to complement DDI strategies. We systematically evaluate emerging candidates including PCNA inhibitors, HDAC inhibitors, and carbonic anhydrase inhibitors, focusing on their ability to modulate the tumor microenvironment and enhance immunotherapy responses. This \"DDI + 1\" approach targets alternative pathways to overcome resistance mechanisms and expand treatment efficacy to traditionally immunotherapy-resistant cancers. Through comprehensive analysis of preclinical evidence and ongoing clinical trials, we address critical challenges in immunotherapy, including primary and acquired resistance, cold tumor conversion, and pathway exhaustion. The review synthesizes current findings while proposing innovative solutions and future research directions. Our framework demonstrates how strategic integration of multiple immune-based approaches can significantly improve therapeutic outcomes across diverse cancer types, potentially revolutionizing cancer treatment paradigms. This concept of DDI, enhanced by rational third-agent selection, represents a promising direction for addressing urgent clinical needs in oncology. By establishing a theoretical foundation for this approach, we aim to guide future research and clinical applications in cancer immunotherapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"114"},"PeriodicalIF":13.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191524","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":"Overall survival of recurrent/metastatic head & neck squamous cell carcinoma patients progressing after ≥ 1 line of systemic therapy, treated with MVX-ONCO-1, a novel, first in class cell encapsulation-based immunotherapy: results of SAKK 11/16, a phase IIa trial.","authors":"Eugenio Fernandez, Rémi Vernet, Muriel Urwyler, Olivier Von Rohr, Emily Charrier, Marie-Claude Belkouch, Valentin Saingier, Fabien Courtout, Claudio DeVito, Virginie Ancrenaz, Nicolas Dulguerov, Wolfram Karenovics, Julien Grogg, Jessica Renaux, Katrin Gobat, Gisela Müller, Tomas Brezina, Tamara Rordorf, Markus Joerger, Olivier Michielin, Jean Villard, Nicolas Mach","doi":"10.1186/s40164-025-00703-x","DOIUrl":"10.1186/s40164-025-00703-x","url":null,"abstract":"<p><strong>Background: </strong>Over the past two decades, most cancer vaccines have failed to be developed clinically. The lack of efficient priming with specific tumor antigens and/or weak adjuvants may explain this poor success rate. MVX-ONCO-1, a personalized cell-based vaccine, combines inactivated autologous tumor cells and encapsulated allogeneic human cells genetically engineered to produce granulocyte-macrophage colony stimulating factor (GM-CSF). This unique technology allows sustained local delivery of strong adjuvant at the vaccination site. The combination of inactivated autologous tumor cells and potent local adjuvant delivery addresses these two unmet critical steps and may recapitulate in patients the successful combination observed in experimental models.</p><p><strong>Methods: </strong>The SAKK 11/16, a Phase IIa trial with Overall Survival (OS) as the primary endpoint was the first efficacy study evaluating MVX-ONCO-1. Patients with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) progressing after at least one line of systemic therapy were enrolled with 50% of patients alive at 26 weeks as the primary objective.</p><p><strong>Results: </strong>In this hard-to-treat population, SAKK 11/16 met the primary endpoint, with 68.8% of patients alive at 6 months. The median OS was 11.4 months, with 32% of the patients alive after 18 months. Complete and partial responses were observed on MVX-ONCO-1 monotherapy. Moreover, all patients who developed a positive DTH reaction to their tumor cells upon vaccination survived at 12 months. Additionally, patients living for more than 12 months had higher circulating antibody titers against tumor-associated antigens. Explorative analysis looking at median OS from the start of anti-PD-1 therapy was 21.7 months. In addition, no new safety signals with no systemic adverse events (AE) related to the treatment and no manufacturing issues were observed in this multicenter trial.</p><p><strong>Conclusions: </strong>These findings suggest that MVX-ONCO-1 can induce a coordinated immune response with clinical benefits as a standalone treatment, leading to prolonged survival. This effect may be enhanced by previous exposure to immune checkpoint inhibitors. Trial registration (ClinicalTrials.gov): NCT02999646.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"113"},"PeriodicalIF":13.5,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947907","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":"IL-7-PD-L1 nano-antibody mediated \"zipper\" effect augments the tumoricidal activity of tumor-infiltrating lymphocytes.","authors":"Zhongjie Yu, Zhen Guo, Bin Jiang, Yueshu Zhu, Lin Shao, Xinhua Zhang, Yi Zhao, Di Wu, Aotian Xu","doi":"10.1186/s40164-025-00702-y","DOIUrl":"10.1186/s40164-025-00702-y","url":null,"abstract":"<p><p>Cancer represents a pressing global health concern, characterized by a substantial number of unmet clinical needs. Cell therapy has emerged as a promising and efficacious approach for cancer treatment, particularly tumor-infiltrating lymphocytes (TILs), which have demonstrated remarkable improvements in patients' overall survival rates across various clinical studies. However, the tumor microenvironment exerts a adverse effect on TILs, leading to their rapid exhaustion and functional disorder. Consequently, this impedes their ability to effectively eradicate tumors and thus hinders the achievement of the anticipated therapeutic efficacy. Here, we employed lentiviral vector-mediated genetic engineering to manipulate TILs for the expression of TIGIT shRNA, IL-7-PD-L1 nano-antibody fusion protein, and the 'molecular switch' HuEGFRt. The engineered TILs exhibited higher viability, reinforced cell expansion, and reduced reliance on IL-2. The stem-like proportion of engineered TILs is significantly augmented, and their activation level is enhanced when co-cultured with tumor cells. Meanwhile, the engineered TILs exert sustained cytotoxicity after repeated stimulation from tumor cells. The use of Cetuximab has been demonstrated in vitro to induce specific apoptosis of engineered TILs through HuEGFRt, thereby ensuring safety throughout the treatment process. In the mouse tumor model, following infusion of engineered TILs, the tumor volume significantly reduced, once again demonstrating the effectiveness of engineered TILs. The findings of our study demonstrate the exceptional performance of engineered TILs, which undoubtedly holds great promise for the clinical application of engineered TILs, ultimately benefiting a larger population of cancer patients.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"112"},"PeriodicalIF":13.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947952","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}