Cancer continues to be a major global health burden, with high morbidity and mortality. Building on the success of immune checkpoint inhibitors and adoptive cellular therapy, cancer vaccines have garnered significant interest, but their clinical success remains modest. Benefiting from advancements in technology, many meticulously designed cancer vaccines have shown promise, warranting further investigations to reach their full potential. Cancer vaccines hold unique benefits, particularly for patients resistant to other therapies, and they offer the ability to initiate broad and durable T cell responses. In this review, we highlight the antigen selection for cancer vaccines, introduce the immune responses induced by vaccines, and propose strategies to enhance vaccine immunogenicity. Furthermore, we summarize key features and notable clinical advances of various vaccine platforms. Lastly, we delve into the mechanisms of tumor resistance and explore the potential benefits of combining cancer vaccines with standard treatments and other immunomodulatory approaches to improve vaccine efficacy.
{"title":"Cancer vaccines: current status and future directions","authors":"Yingqiong Zhou, Yuquan Wei, Xiaohe Tian, Xiawei Wei","doi":"10.1186/s13045-025-01670-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01670-w","url":null,"abstract":"Cancer continues to be a major global health burden, with high morbidity and mortality. Building on the success of immune checkpoint inhibitors and adoptive cellular therapy, cancer vaccines have garnered significant interest, but their clinical success remains modest. Benefiting from advancements in technology, many meticulously designed cancer vaccines have shown promise, warranting further investigations to reach their full potential. Cancer vaccines hold unique benefits, particularly for patients resistant to other therapies, and they offer the ability to initiate broad and durable T cell responses. In this review, we highlight the antigen selection for cancer vaccines, introduce the immune responses induced by vaccines, and propose strategies to enhance vaccine immunogenicity. Furthermore, we summarize key features and notable clinical advances of various vaccine platforms. Lastly, we delve into the mechanisms of tumor resistance and explore the potential benefits of combining cancer vaccines with standard treatments and other immunomodulatory approaches to improve vaccine efficacy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1186/s13045-025-01669-3
Roman M Shapiro, Michal Sheffer, Matthew A Booker, Michael Y Tolstorukov, Grace C Birch, Moshe Sade-Feldman, Jacy Fang, Shuqiang Li, Wesley Lu, Michela Ansuinelli, Remy Dulery, Mubin Tarannum, Joanna Baginska, Nishant Dwivedi, Ashish Kothari, Livius Penter, Yasmin Z Abdulhamid, Isabel E Kaplan, Dinh Khanhlinh, Ravindra Uppaluri, Robert A Redd, Sarah Nikiforow, John Koreth, Jerome Ritz, Catherine J Wu, Robert J Soiffer, Glenn J Hanna, Rizwan Romee
Background: Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.
Methods: We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo.
Results: The primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8+ T cells, and subsequent accelerated rejection of donor NK cells.
Conclusions: CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI.
Trial registration: NCT04290546.
{"title":"First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer.","authors":"Roman M Shapiro, Michal Sheffer, Matthew A Booker, Michael Y Tolstorukov, Grace C Birch, Moshe Sade-Feldman, Jacy Fang, Shuqiang Li, Wesley Lu, Michela Ansuinelli, Remy Dulery, Mubin Tarannum, Joanna Baginska, Nishant Dwivedi, Ashish Kothari, Livius Penter, Yasmin Z Abdulhamid, Isabel E Kaplan, Dinh Khanhlinh, Ravindra Uppaluri, Robert A Redd, Sarah Nikiforow, John Koreth, Jerome Ritz, Catherine J Wu, Robert J Soiffer, Glenn J Hanna, Rizwan Romee","doi":"10.1186/s13045-025-01669-3","DOIUrl":"10.1186/s13045-025-01669-3","url":null,"abstract":"<p><strong>Background: </strong>Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.</p><p><strong>Methods: </strong>We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo.</p><p><strong>Results: </strong>The primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8<sup>+</sup> T cells, and subsequent accelerated rejection of donor NK cells.</p><p><strong>Conclusions: </strong>CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI.</p><p><strong>Trial registration: </strong>NCT04290546.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"18 1","pages":"17"},"PeriodicalIF":29.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414445","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}
Pub Date : 2025-02-07DOI: 10.1186/s13045-025-01668-4
HyunJun Kang, Dinh Hoa Hoang, Melissa Valerio, Khyatiben Pathak, William Graff, Alexis LeVee, Jun Wu, Mark A. LaBarge, David Frankhouser, Russell C. Rockne, Patrick Pirrotte, Bin Zhang, Joanne Mortimer, Le Xuan Truong Nguyen, Guido Marcucci
Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.
{"title":"Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells","authors":"HyunJun Kang, Dinh Hoa Hoang, Melissa Valerio, Khyatiben Pathak, William Graff, Alexis LeVee, Jun Wu, Mark A. LaBarge, David Frankhouser, Russell C. Rockne, Patrick Pirrotte, Bin Zhang, Joanne Mortimer, Le Xuan Truong Nguyen, Guido Marcucci","doi":"10.1186/s13045-025-01668-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01668-4","url":null,"abstract":"Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1186/s13045-025-01666-6
Gang Chen, Dong-Chen Sun, Yi Ba, Ya-Xiong Zhang, Ting Zhou, Yuan-Yuan Zhao, Hong-Yun Zhao, Wen-Feng Fang, Yan Huang, Zhen Wang, Chao Deng, De-Sheng Hu, Wei Wang, Jin-Guan Lin, Gui-Ling Li, Su-Xia Luo, Zhi-Chao Fu, Hai-Sheng Zhu, Hui-Li Wang, Sheng-Li Cai, Xiao-Qiang Kang, Li Zhang, Yun-Peng Yang
Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.
{"title":"Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial","authors":"Gang Chen, Dong-Chen Sun, Yi Ba, Ya-Xiong Zhang, Ting Zhou, Yuan-Yuan Zhao, Hong-Yun Zhao, Wen-Feng Fang, Yan Huang, Zhen Wang, Chao Deng, De-Sheng Hu, Wei Wang, Jin-Guan Lin, Gui-Ling Li, Su-Xia Luo, Zhi-Chao Fu, Hai-Sheng Zhu, Hui-Li Wang, Sheng-Li Cai, Xiao-Qiang Kang, Li Zhang, Yun-Peng Yang","doi":"10.1186/s13045-025-01666-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01666-6","url":null,"abstract":"Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"48 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1186/s13045-025-01667-5
Seungyeul Yoo, Ayushi S. Patel, Sarah Karam, Yi Zhong, Li Wang, Feng Jiang, Ranran Kong, Sharon Bikvan, Wenhui Wang, Abhilasha Sinha, Charles A. Powell, Jun Zhu, Hideo Watanabe
Small cell lung cancer (SCLC) is an aggressive and heterogeneous subtype, representing 15% of lung cancer cases. Although SCLC initially responds to etoposide and platinum (EP) chemotherapy, nearly all patients relapse with resistant tumors. While recent advances in immunotherapy have shown promise, only 10–20% of patients benefit, and effective stratification methods are lacking. The mechanisms of resistance to both therapeutics remain obscure. In this study, we aimed to gain insights into those leveraging a recent surge in the field of SCLC genomics. We constructed a regulatory network for SCLC and identified granulin precursor (GRN) as a hub of EP response associated genes. GRN-low patients showed improved survival with chemotherapy, while GRN-high patients exhibited resistance. GRN overexpression in SCLC cells conferred resistance to EP treatment and suppressed neuroendocrine features. GRN and its associated genes were linked to cancer cell intrinsic immunogenicity, and single-cell RNA-seq data revealed that GRN expression is particularly high in subsets of tumor-associated macrophages. In concordance with these findings, GRN-low tumors showed significantly better survival with chemo-immunotherapy, while GRN-high tumors did not benefit from additional immunotherapy. GRN-high tumors, associated with non-neuroendocrine (non-NE) subtypes, had a higher level of macrophage infiltration, potentially contributing to immunotherapy resistance. These results highlight GRN as a critical regulator of chemo-resistance and a potential biomarker for immunotherapy resistance in SCLC. Targeted therapeutic strategies for GRN-low patients could improve outcomes, while new approaches are needed for GRN-high patients. Overall, our findings implicate GRN as a bridge between chemotherapy and immunotherapy resistance through GRN-mediated mechanisms.
{"title":"Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer","authors":"Seungyeul Yoo, Ayushi S. Patel, Sarah Karam, Yi Zhong, Li Wang, Feng Jiang, Ranran Kong, Sharon Bikvan, Wenhui Wang, Abhilasha Sinha, Charles A. Powell, Jun Zhu, Hideo Watanabe","doi":"10.1186/s13045-025-01667-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01667-5","url":null,"abstract":"Small cell lung cancer (SCLC) is an aggressive and heterogeneous subtype, representing 15% of lung cancer cases. Although SCLC initially responds to etoposide and platinum (EP) chemotherapy, nearly all patients relapse with resistant tumors. While recent advances in immunotherapy have shown promise, only 10–20% of patients benefit, and effective stratification methods are lacking. The mechanisms of resistance to both therapeutics remain obscure. In this study, we aimed to gain insights into those leveraging a recent surge in the field of SCLC genomics. We constructed a regulatory network for SCLC and identified granulin precursor (GRN) as a hub of EP response associated genes. GRN-low patients showed improved survival with chemotherapy, while GRN-high patients exhibited resistance. GRN overexpression in SCLC cells conferred resistance to EP treatment and suppressed neuroendocrine features. GRN and its associated genes were linked to cancer cell intrinsic immunogenicity, and single-cell RNA-seq data revealed that GRN expression is particularly high in subsets of tumor-associated macrophages. In concordance with these findings, GRN-low tumors showed significantly better survival with chemo-immunotherapy, while GRN-high tumors did not benefit from additional immunotherapy. GRN-high tumors, associated with non-neuroendocrine (non-NE) subtypes, had a higher level of macrophage infiltration, potentially contributing to immunotherapy resistance. These results highlight GRN as a critical regulator of chemo-resistance and a potential biomarker for immunotherapy resistance in SCLC. Targeted therapeutic strategies for GRN-low patients could improve outcomes, while new approaches are needed for GRN-high patients. Overall, our findings implicate GRN as a bridge between chemotherapy and immunotherapy resistance through GRN-mediated mechanisms.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1186/s13045-025-01662-w
Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber
<p><b>Correction: Journal of Hematology & Oncology (2024) 17:104</b> <b>https://doi.org/10.1186/s13045-024-01622-w</b></p><p>The authors wish to note the following amendments to the affiliations and the funding in the original article.</p><br/><p>The affiliations should instead be as follows:</p><p>• Wael Saber:</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><p>• Paul Auer:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>Cancer Center Biostatistics Shared Resource, Medical College of Wisconsin, Milwaukee, WI</p><p>• Zhongyuan Chen:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>The Funding should instead read as follows:</p><p>Jing Dong is supported by the NHLBI (K01 HL164972) and the Medical College of Wisconsin Cancer Center. N00014-17-1-2850 from the Office of Naval Research. CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); and N00014-23-1-2057 and N00014-24-1-2057 from the Office of Naval Research. Support is also provided by the Medical College of Wisconsin, NMDP, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Medac GmbH; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, In
{"title":"Correction: Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation","authors":"Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber","doi":"10.1186/s13045-025-01662-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01662-w","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2024) 17:104</b> <b>https://doi.org/10.1186/s13045-024-01622-w</b></p><p>The authors wish to note the following amendments to the affiliations and the funding in the original article.</p><br/><p>The affiliations should instead be as follows:</p><p>• Wael Saber:</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><p>• Paul Auer:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>Cancer Center Biostatistics Shared Resource, Medical College of Wisconsin, Milwaukee, WI</p><p>• Zhongyuan Chen:</p><br/><p>Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI</p><br/><p>CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI</p><br/><p>The Funding should instead read as follows:</p><p>Jing Dong is supported by the NHLBI (K01 HL164972) and the Medical College of Wisconsin Cancer Center. N00014-17-1-2850 from the Office of Naval Research. CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); and N00014-23-1-2057 and N00014-24-1-2057 from the Office of Naval Research. Support is also provided by the Medical College of Wisconsin, NMDP, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Medac GmbH; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, In","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"61 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression. On one hand, m7G modification-associated modulate tumour progression and affect malignant biological characteristics, including sustained proliferation signalling, resistance to cell death, activation of invasion and metastasis, reprogramming of energy metabolism, genome instability, and immune evasion. This suggests that they may be novel therapeutic targets for cancer treatment. On the other hand, the aberrant expression of m7G modification-associated molecules is linked to clinicopathological characteristics, including tumour staging, lymph node metastasis, and unfavourable prognoses in patients with cancer, indicating their potential as tumour biomarkers. This review consolidates the discovery, identification, detection methodologies, and functional roles of m7G modification, analysing the mechanisms by which m7G modification-associated molecules contribute to tumour development, and exploring their potential clinical applications in cancer diagnostics and therapy, thereby providing innovative strategies for tumour identification and targeted treatment.
{"title":"N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential","authors":"Qihui Wu, Xiaodan Fu, Guoqian Liu, Xiaoyun He, Yimin Li, Chunlin Ou","doi":"10.1186/s13045-025-01665-7","DOIUrl":"https://doi.org/10.1186/s13045-025-01665-7","url":null,"abstract":"N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression. On one hand, m7G modification-associated modulate tumour progression and affect malignant biological characteristics, including sustained proliferation signalling, resistance to cell death, activation of invasion and metastasis, reprogramming of energy metabolism, genome instability, and immune evasion. This suggests that they may be novel therapeutic targets for cancer treatment. On the other hand, the aberrant expression of m7G modification-associated molecules is linked to clinicopathological characteristics, including tumour staging, lymph node metastasis, and unfavourable prognoses in patients with cancer, indicating their potential as tumour biomarkers. This review consolidates the discovery, identification, detection methodologies, and functional roles of m7G modification, analysing the mechanisms by which m7G modification-associated molecules contribute to tumour development, and exploring their potential clinical applications in cancer diagnostics and therapy, thereby providing innovative strategies for tumour identification and targeted treatment.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"84 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-24DOI: 10.1186/s13045-025-01663-9
Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Reinhard Schnettler, Kim de Veirman, Thaqif El Khassawna, Christian Heiss, Anne Hild, Daniel Zahner, Francisca Alagboso, Anja Henss, Susanne Beck, Martina Emde-Rajaratnam, Jürgen Burhenne, Juliane Bamberger, Eline Menu, Elke de Bruyne, Michael Gelinsky, Marian Kampschulte, Marcus Rohnke, Sabine Wenisch, Karin Vanderkerken, Thomas Hanke, Anja Seckinger, Volker Alt
<p><b>Journal of Hematology & Oncology (2024) 17:128</b></p><p><b>https://doi.org/10.1186/s13045-024-01636-4</b></p><p>The original article mistakenly omitted last author, Volker Alt as a co-Corresponding Author due to an error mistakenly carried forward by the production team.</p><p>Dr. Alt has since been restored as co-Corresponding Author.</p><span>Author notes</span><ol><li><p>Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Thomas Hanke, Anja Seckinger and Volker Alt have contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Laboratory of Hematology and Immunology & Labor für Myelomforschung, Vrije Universiteit Brussel, Laarbeeklaan 103, Jette, 1090, Belgium</p><p>Dirk Hose, Ulrich Thormann, Kim de Veirman, Susanne Beck, Martina Emde-Rajaratnam, Eline Menu, Elke de Bruyne, Karin Vanderkerken & Anja Seckinger</p></li><li><p>Experimentelle Unfallchirurgie (ForMED), Justus-Liebig-Universität Gießen, Aulweg 128, 35392, Gießen, Germany</p><p>Seemun Ray, Thaqif El Khassawna, Christian Heiss, Francisca Alagboso & Volker Alt</p></li><li><p>Institut für Werkstoffwissenschaft, Max-Bergmann-Zentrum für Biomaterialien, Technische Universität Dresden, Budapester Straße 27, 01069, Dresden, Germany</p><p>Sina Rößler & Thomas Hanke</p></li><li><p>Justus-Liebig-Universität Gießen, Ludwigstraße 23, 35392, Gießen, Germany</p><p>Reinhard Schnettler & Daniel Zahner</p></li><li><p>Klinische Anatomie und Experimentelle Chirurgie C/O Institut für Veterinär-Anatomie, -Histologie und - Embryologie, Justus-Liebig-Universität Gießen, Frankfurter Straße 98, 35392, Gießen, Germany</p><p>Anne Hild & Sabine Wenisch</p></li><li><p>I. Physikalisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 16, 35392, Gießen, Germany</p><p>Anja Henss</p></li><li><p>Innere Medizin IX - Abteilung für Klinische Pharmakologie und Pharmakoepidemiologie, Medizinische Fakultät/Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany</p><p>Jürgen Burhenne</p></li><li><p>Labor Für Experimentelle Radiologie, Justus-Liebig-Universität Gießen, Carl-Maria-von-Weber-Straße 8, 35392, Gießen, Germany</p><p>Juliane Bamberger & Marian Kampschulte</p></li><li><p>Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany</p><p>Michael Gelinsky</p></li><li><p>Physikalisch-Chemisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 17, 35392, Gießen, Germany</p><p>Marcus Rohnke</p></li><li><p>Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany</p><p>Volker Alt</p></li></ol><span>Authors</span><ol><li><span>Dirk Hose</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Seemun Ray</span>View author publications<p>You can also search f
{"title":"Correction: Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma","authors":"Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Reinhard Schnettler, Kim de Veirman, Thaqif El Khassawna, Christian Heiss, Anne Hild, Daniel Zahner, Francisca Alagboso, Anja Henss, Susanne Beck, Martina Emde-Rajaratnam, Jürgen Burhenne, Juliane Bamberger, Eline Menu, Elke de Bruyne, Michael Gelinsky, Marian Kampschulte, Marcus Rohnke, Sabine Wenisch, Karin Vanderkerken, Thomas Hanke, Anja Seckinger, Volker Alt","doi":"10.1186/s13045-025-01663-9","DOIUrl":"https://doi.org/10.1186/s13045-025-01663-9","url":null,"abstract":"<p><b>Journal of Hematology & Oncology (2024) 17:128</b></p><p><b>https://doi.org/10.1186/s13045-024-01636-4</b></p><p>The original article mistakenly omitted last author, Volker Alt as a co-Corresponding Author due to an error mistakenly carried forward by the production team.</p><p>Dr. Alt has since been restored as co-Corresponding Author.</p><span>Author notes</span><ol><li><p>Dirk Hose, Seemun Ray, Sina Rößler, Ulrich Thormann, Thomas Hanke, Anja Seckinger and Volker Alt have contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Laboratory of Hematology and Immunology & Labor für Myelomforschung, Vrije Universiteit Brussel, Laarbeeklaan 103, Jette, 1090, Belgium</p><p>Dirk Hose, Ulrich Thormann, Kim de Veirman, Susanne Beck, Martina Emde-Rajaratnam, Eline Menu, Elke de Bruyne, Karin Vanderkerken & Anja Seckinger</p></li><li><p>Experimentelle Unfallchirurgie (ForMED), Justus-Liebig-Universität Gießen, Aulweg 128, 35392, Gießen, Germany</p><p>Seemun Ray, Thaqif El Khassawna, Christian Heiss, Francisca Alagboso & Volker Alt</p></li><li><p>Institut für Werkstoffwissenschaft, Max-Bergmann-Zentrum für Biomaterialien, Technische Universität Dresden, Budapester Straße 27, 01069, Dresden, Germany</p><p>Sina Rößler & Thomas Hanke</p></li><li><p>Justus-Liebig-Universität Gießen, Ludwigstraße 23, 35392, Gießen, Germany</p><p>Reinhard Schnettler & Daniel Zahner</p></li><li><p>Klinische Anatomie und Experimentelle Chirurgie C/O Institut für Veterinär-Anatomie, -Histologie und - Embryologie, Justus-Liebig-Universität Gießen, Frankfurter Straße 98, 35392, Gießen, Germany</p><p>Anne Hild & Sabine Wenisch</p></li><li><p>I. Physikalisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 16, 35392, Gießen, Germany</p><p>Anja Henss</p></li><li><p>Innere Medizin IX - Abteilung für Klinische Pharmakologie und Pharmakoepidemiologie, Medizinische Fakultät/Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany</p><p>Jürgen Burhenne</p></li><li><p>Labor Für Experimentelle Radiologie, Justus-Liebig-Universität Gießen, Carl-Maria-von-Weber-Straße 8, 35392, Gießen, Germany</p><p>Juliane Bamberger & Marian Kampschulte</p></li><li><p>Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany</p><p>Michael Gelinsky</p></li><li><p>Physikalisch-Chemisches Institut, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 17, 35392, Gießen, Germany</p><p>Marcus Rohnke</p></li><li><p>Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany</p><p>Volker Alt</p></li></ol><span>Authors</span><ol><li><span>Dirk Hose</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Seemun Ray</span>View author publications<p>You can also search f","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"13 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-23DOI: 10.1186/s13045-024-01654-2
Yantao Duan, Yonghu Xu, Yi Dou, Dazhi Xu
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world’s population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis—key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori’s role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
{"title":"Helicobacter pylori and gastric cancer: mechanisms and new perspectives","authors":"Yantao Duan, Yonghu Xu, Yi Dou, Dazhi Xu","doi":"10.1186/s13045-024-01654-2","DOIUrl":"https://doi.org/10.1186/s13045-024-01654-2","url":null,"abstract":"Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world’s population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis—key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori’s role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-23DOI: 10.1186/s13045-025-01661-x
Zwi N. Berneman, Maxime De Laere, Paul Germonpré, Manon T. Huizing, Yannick Willemen, Eva Lion, Hans De Reu, Jolien Van den Bossche, Jan Van den Brande, Pol Specenier, Sevilay Altintas, Peter A. van Dam, Nathalie Cools, Griet Nijs, Barbara Stein, Kim Caluwaerts, Annemiek Snoeckx, Bart Op de Beeck, Kirsten Saevels, Lynn Rutsaert, Irma Vandenbosch, Gizem Oner, Martin Lammens, Pierre Van Damme, Sian Llewellyn-Lacey, David A. Price, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama, Marie M. Couttenye, Ann L. Van de Velde, Viggo F. Van Tendeloo, Marc Peeters, Sébastien Anguille, Evelien L.J.M. Smits
Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms’ tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.
{"title":"WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome","authors":"Zwi N. Berneman, Maxime De Laere, Paul Germonpré, Manon T. Huizing, Yannick Willemen, Eva Lion, Hans De Reu, Jolien Van den Bossche, Jan Van den Brande, Pol Specenier, Sevilay Altintas, Peter A. van Dam, Nathalie Cools, Griet Nijs, Barbara Stein, Kim Caluwaerts, Annemiek Snoeckx, Bart Op de Beeck, Kirsten Saevels, Lynn Rutsaert, Irma Vandenbosch, Gizem Oner, Martin Lammens, Pierre Van Damme, Sian Llewellyn-Lacey, David A. Price, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama, Marie M. Couttenye, Ann L. Van de Velde, Viggo F. Van Tendeloo, Marc Peeters, Sébastien Anguille, Evelien L.J.M. Smits","doi":"10.1186/s13045-025-01661-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01661-x","url":null,"abstract":"Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms’ tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"45 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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