Journal of Hematology & Oncology最新文献

{"title":"Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells","authors":"Michele Pezzella, Concetta Quintarelli, Maria C. Quadraccia, Andrea Sarcinelli, Simona Manni, Laura Iaffaldano, Alessio Ottaviani, Roselia Ciccone, Antonio Camera, Maria L. D’Amore, Stefano Di Cecca, Matilde Sinibaldi, Marika Guercio, Mariasole Aurigemma, Pamela De Falco, Valentina Fustaino, Rossella Rota, Silvia Pomella, Matteo Cassandri, Angela Di Giannatale, Chiara Agrati, Veronica Bordoni, Federica Guarracino, Michele Massa, Giada Del Baldo, Marco Becilli, Giuseppe M. Milano, Francesca Del Bufalo, Franco Locatelli, Biagio De Angelis","doi":"10.1186/s13045-024-01641-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01641-7","url":null,"abstract":"Sarcomas are rare, mesenchymal tumors, representing about 10–15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use of iCasp9.2A.GD2.CAR-CD28.4–1BBζ (CAR.GD2) T-cells as a treatment option for patients who have GD2-positive sarcomas and we sought to identify factors shaping hostile tumor microenvironment in this setting. GD2 expression was evaluated by flow-cytometry on primary tumor biopsies of pediatric sarcoma patients. GD2 expression in sarcoma cells was also evaluated in response to an enhancer of zeste homolog 2 (EZH2) inhibitor (Tazemetostat). The antitumor activity of CAR.GD2 T-cells was evaluated both in vitro and in vivo preclinical models of orthotopic and/or metastatic soft-tissue and bone sarcomas. GD2 expression was detected in 55% of the primary tumors. Notably, the Osteosarcoma and Alveolar Rhabdomyosarcomas subtypes exhibited the highest GD2 expression levels, while Ewing sarcoma showed the lowest. CAR.GD2 T-cells show a significant tumor control both in vitro and in vivo models of GD2-expressing tumors. Pretreatment with an EZH2 inhibitor (Tazemetostat) upregulating GD2 expression, sensitizes GD2dim sarcoma cells to CAR.GD2 T-cells cytotoxic activity. Moreover, in mouse models of disseminated Rhabdomyosarcomas and orthotopic Osteosarcoma, CAR.GD2 T-cells showed both a vigorous anti-tumor activity and long-term persistence as compared to un-transduced T-cells. The presence of immunosuppressive murine myeloid-derived suppressor (MDSC) cells significantly reduces long-term anti-tumour activity of infused CAR.GD2 T-cells. Tumor-derived G-CSF was found to be one of the key factors driving expansion of immunosuppressive murine and human MDSC, thus indirectly limiting the efficacy of CAR.GD2 T-cells. Our preclinical data strongly suggest that CAR.GD2 T-cells hold promise as a potential therapeutic option for the treatment of patients with GD2-positive sarcomas. Strategies to tackle hostile immunosuppressive MDSC are desirable to optimize CAR.GD2 T-cell activity.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"99 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848829","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}

{"title":"myCAF-derived exosomal PWAR6 accelerates CRC liver metastasis via altering glutamine availability and NK cell function in the tumor microenvironment","authors":"Hongsheng Fang, Weixing Dai, Ruiqi Gu, Yanbo Zhang, Jin Li, Wenqin Luo, Shanyou Tong, Lingyu Han, Yichao Wang, Chengyao Jiang, Xue Wang, Renjie Wang, Guoxiang Cai","doi":"10.1186/s13045-024-01643-5","DOIUrl":"https://doi.org/10.1186/s13045-024-01643-5","url":null,"abstract":"Liver metastasis from colorectal cancer (CRC) is a major clinical challenge that severely affects patient survival. myofibroblastic cancer-associated fibroblasts (myCAFs) are a major component of the CRC tumor microenvironment, where they contribute to tumor progression and metastasis through exosomes. Single-cell analysis highlighted a notable increase in myCAFs in colorectal cancer liver metastases (CRLM). Exosomal sequencing identified PWAR6 as the most significantly elevated lncRNA in these metastatic tissues. In vivo and in vitro assays confirmed PWAR6's roles in CRC cell stemness, migration, and glutamine uptake. RNA pulldown, RIP, and Co-IP assays investigated the molecular mechanisms of the PWAR6/NRF2/SLC38A2 signaling axis in CRC progression, flow cytometry was used to assess NK cell activity and cytotoxicity. Clinically, higher PWAR6 expression levels are strongly associated with increased 68Ga FAPI-PET/CT SUVmax values, particularly in CRLM patients, where expression significantly exceeds that of non-LM cases and normal colon tissues. Regression analysis and survival data further support PWAR6 as a negative prognostic marker, with elevated levels correlating with worse patient outcomes. Mechanistically, PWAR6 promotes immune evasion by inhibiting NRF2 degradation through competitive binding with Keap1, thereby upregulating SLC38A2 expression, which enhances glutamine uptake in CRC cells and depletes glutamine availability for NK cells. myCAFs derived exosomes PWAR6 represents a pivotal marker for CRC liver metastasis, and its targeted inhibition with ASO-PWAR6, in combination with FAPI treatment, effectively curtails metastasis in preclinical models, offering promising therapeutic potential for clinical management. ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"13 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848830","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}

{"title":"Engineering a controllable and reversible switch for CAR-based cellular immunotherapies via a genetic code expansion system","authors":"Yue Liu, Lingna An, Xiaoqi Wang, Yueyu Dai, Cheng Zhang, Qin Wen, Xi Zhang","doi":"10.1186/s13045-024-01648-0","DOIUrl":"https://doi.org/10.1186/s13045-024-01648-0","url":null,"abstract":"As one of the most promising adoptive cell therapies, CAR-T cell therapy has achieved notable clinical effects in patients with hematological tumors. However, several treatment-related obstacles remain in CAR-T therapy, such as cytokine release syndrome, neurotoxicity, and high-frequency recurrence, which severely limit the long-term effects and can potentially be fatal. Therefore, strategies to increase the controllability and safety of CAR-T therapy are urgently needed. In this study, we engineered a genetic code expansion-based therapeutic system to achieve rapid CAR protein expression and regulation in response to cognate unnatural amino acids at the translational level. When the unnatural amino acid N-ε-((tert-butoxy) carbonyl)-l-lysine (BOCK) is absent, the CAR protein cannot be completely translated, and CAR-T is “closed”. When BOCK is present, complete translation of the CAR protein is induced, and CAR-T is “open”. Therefore, we investigated whether the BOCK-induced device can control CAR protein expression and regulate CAR-T cell function using a series of in vitro and in vivo experiments. First, we verified that the BOCK-induced genetic code expansion system enables the regulation of protein expression as a controllable switch. We subsequently demonstrated that when the system was combined with CAR-T cells, BOCK could effectively and precisely control CAR protein expression and induce CAR signaling activation. When incubated with tumor cells, BOCK regulated CAR-T cells cytotoxicity in a dose-dependent manner. Our results revealed that the presence of BOCK enables the activation of CAR-T cells with strong anti-tumor cytotoxicity in a NOG mouse model. Furthermore, we verified that the BOCK-induced CAR device provided NK cells with controllable anti-tumor activity, which confirmed the universality of this device. Our study systematically demonstrated that the BOCK-induced genetic code expansion system effectively and precisely regulates CAR protein expression and controls CAR-T cell anti-tumor effects in vitro and in vivo. We conclude that this controllable and reversible switch has the potential for more effective, secure, and clinically available CAR-based cellular immunotherapies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"260 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848834","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}

{"title":"Recent advances in sarcoma therapy: new agents, strategies and predictive biomarkers","authors":"Minggui Pan, Maggie Zhou, Lu Xie, Nam Bui, Kristen Ganjoo","doi":"10.1186/s13045-024-01650-6","DOIUrl":"https://doi.org/10.1186/s13045-024-01650-6","url":null,"abstract":"Soft tissue and bone sarcomas are a heterogenous group of uncommon mesenchymal tumors with high unmet needs for novel therapeutic and diagnostic strategies. Despite many challenges that persist, innovative therapeutics are emerging. Here we provide a review of the studies presented at the 2024 American Society of Clinical Oncology annual meeting that were focused on sarcoma. There were many outstanding studies that were reported at the meeting. We begin by discussing the clinical studies on soft tissue sarcoma (STS) that included multiple histology subtypes, followed by highlighting developments in cellular therapy, before delving into specific STS histologic subtypes followed by a section covering the studies that were focused on predictive biomarkers. We conclude by discussing the studies in bone sarcomas. Some of the studies discussed here are likely to be practice changing. Some of the early-phase clinical trials have shown encouraging results.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"51 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848832","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}

{"title":"Safety and efficacy of amulirafusp alfa (IMM0306), a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a phase 1/2 study","authors":"Jianliang Yang, Yongping Song, Keshu Zhou, Zhiming Li, Mingzhi Zhang, Hongmei Jing, Zhen Wang, Li Yu, Wei Meng, Qiying Lu, Wenzhi Tian, Yuankai Shi","doi":"10.1186/s13045-024-01646-2","DOIUrl":"https://doi.org/10.1186/s13045-024-01646-2","url":null,"abstract":"Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles. The primary endpoints were to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of amulirafusp alfa. Between May 22, 2020 and February 10, 2022, 48 patients with r/r B-NHL were enrolled and received amulirafusp alfa at the doses of 40–2000 μg/kg. As of the data cut-off date of April 18, 2024, no dose-limiting toxicity was observed, and the MTD was not reached. The dose of 2000 μg/kg was identified as the RP2D. All grades and ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 48 (100%) and 33 (68.8%) patients, respectively. The most common ≥ grade 3 TRAEs were lymphocyte count decreased (28/48, 58.3%), white blood cell count decreased (10/48, 20.8%), absolute neutrophil count decreased (9/48, 18.8%) and anemia (5/48, 10.4%). At the doses of 800–2000 μg/kg, objective response rate in follicular lymphoma and marginal zone lymphoma was 41.2% (7/17, 95% confidence interval [CI] 18.4–67.1) and 33.3% (2/6, 95% CI 3.7–71.0), respectively. Amulirafusp alfa showed favorable safety profile and preliminary efficacy in patients with r/r B-NHL, meriting further investigation. Trial registration NCT05805943.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"23 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848833","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}

{"title":"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/s13045-024-01636-4","DOIUrl":"https://doi.org/10.1186/s13045-024-01636-4","url":null,"abstract":"Accumulation of malignant plasma cells in the bone marrow causes lytic bone lesions in 80% of multiple myeloma patients. Frequently fracturing, they are challenging to treat surgically. Myeloma cells surviving treatment in the presumably protective environment of bone lesions impede their healing by continued impact on bone turnover and can explain regular progression of patients without detectable minimal residual disease (MRD). Locally applicable biomaterials could stabilize and foster healing of bone defects, simultaneously delivering anti-cancer compounds at systemically intolerable concentrations, overcoming drug resistance. We developed silica-collagen xerogels (sicXer) and bortezomib-releasing silica-collagen xerogels (boXer) for local treatment of osteolytic bone disease and MRD. In vitro and in vivo (tissue sections) release of bortezomib was assessed by ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Material impact on bone formation was assessed in vitro regarding osteoclast/osteoblast numbers and activity. In vivo, drilling defects in a rat- and the 5T33-myeloma mouse model were treated by both materials and assessed by immunohistochemistry, UPLC-MS/MS, µCT, and ToF-SIMS. The material’s anti-myeloma activity was assessed using ten human myeloma cell lines (HMCLs) and eight primary myeloma cell samples including four patients refractory to systemic bortezomib treatment. sicXer and boXer show primary stability comparable to trabecular bone. Granule size and preparation method tailor degradation as indicated by release of the xerogel components (silica and collagen) and bortezomib into culture medium. In vitro, both materials reduce osteoclast activity and do not negatively interfere with osteoblast differentiation and function. The presumed resulting net bone formation with maintained basic remodeling properties was validated in vivo in a rat bone defect model, showing significantly enhanced bone formation for boXer compared to non-treated defects. Both materials induce myeloma cell apoptosis in all HMCLs and primary myeloma cell samples. In the 5T33-myeloma mouse model, both materials stabilized drilling defects and locally controlled malignant plasma cell growth. The combination of stabilization of fracture-prone lesions, stimulation of bone healing, and anti-tumor effect suggest clinical testing of sicXer and boXer as part of a combined systemic/local treatment strategy in multiple myeloma and non-malignant diseases.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"87 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848828","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}

{"title":"Correction: CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells","authors":"Ulrike Erb, Amelie Pajip Megaptche, Xiaoyu Gu, Markus W. Büchler, Margot Zöller","doi":"10.1186/s13045-024-01652-4","DOIUrl":"https://doi.org/10.1186/s13045-024-01652-4","url":null,"abstract":"<p><b>Correction: Journal of Hematology &amp; Oncology 2014, 7:29</b></p><p><b>https://doi.org/10.1186/1756-8722-7-29</b></p><p> Unfortunately, in Fig. 2A in the original article, the same immunohistochemistry image was inadvertently inserted for negative control of EL4-v10 bearing mice treated with either IM7 or K926 as published. The image was mistakenly doubled in Fig. 2A during graphical figure assembly. The error was unintended and the authors sincerely apologize for this oversight.</p><p> The revised and correct Fig. 2A appears below. The authors sincerely apologize for this oversight. I was able to identify the correct image from our archived files as indicated in the attachment with the highlighted image.</p><p> The authors apologize for this error and would like to emphasize that this does not change the scientific conclusions of the article in any way.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-024-01652-4/MediaObjects/13045_2024_1652_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"870\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-024-01652-4/MediaObjects/13045_2024_1652_Fig2_HTML.png\" width=\"685\"/></picture><p>.</p></figure><h3>Authors and Affiliations</h3><ol><li><p>Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany</p><p>Ulrike Erb, Amelie Pajip Megaptche, Xiaoyu Gu &amp; Margot Zöller</p></li><li><p>University Hospital of Surgery, Heidelberg, Germany</p><p>Markus W. Büchler</p></li></ol><span>Authors</span><ol><li><span>Ulrike Erb</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Amelie Pajip Megaptche</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xiaoyu Gu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Markus W. Büchler</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Margot Zöller</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Corresponding author</h3><p>Correspondence to Margot Zöller.</p><h3>Publisher’s note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p>The online version of the original article can be found at https://doi.org/10.1186/1756-8722-7-29</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as yo","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"82 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832006","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}

{"title":"Advances in CAR-T cell therapy for hematologic and solid malignancies: latest updates from 2024 ESMO Congress","authors":"Huageng Huang, Le Yu, Huawei Weng, Wei Zhang, Zhao Wang, Lin Wang, He Huang","doi":"10.1186/s13045-024-01639-1","DOIUrl":"https://doi.org/10.1186/s13045-024-01639-1","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell therapy has emerged as one of the most rapidly evolving modalities of immunotherapy, with substantial success in the treatment of hematological malignancies and encouraging outcomes in solid tumors. Yet, the efficacy of CAR-T therapy is hindered by challenges such as suboptimal expansion and persistence, adverse events, a scarcity of ideal targets, high immunosuppression, and insufficient infiltration due to the intricate tumor microenvironment, all of which limit its application. The 2024 European Society for Medical Oncology (ESMO) Congress presented novel CAR-T cell therapies for hematologic and solid malignancies, focusing on strategies such as cytokine modulation, innovative targets, allogeneic development, mRNA vaccine synergy, in vivo delivery and conditional activation to surmount these challenges.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"74 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776689","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}

{"title":"Global burden of cancer and associated risk factors in 204 countries and territories, 1980–2021: a systematic analysis for the GBD 2021","authors":"Zenghong Wu, Fangnan Xia, Rong Lin","doi":"10.1186/s13045-024-01640-8","DOIUrl":"https://doi.org/10.1186/s13045-024-01640-8","url":null,"abstract":"Cancer is the second most common cause of death globally. Therefore, it is imperative to investigate cancer incidence, mortality rates, and disability-adjusted life years (DALYs) to enhance preventive measures and healthcare resource allocation. This study aimed to assess cancer burden and associated risk factors in 204 countries and territories between 1980 and 2021. We selected data on cancer incidence and mortality rates and associated risk factors from the global burden of disease (GBD) study tool for 204 countries and territories from 1990 to 2021 and 1980 to 2021. We estimated the age-standardized incidence (ASIR) and age-standardized deaths (ASDR) of 34 cancer types categorized as level 3 causes based on the GBD hierarchy. In 2021, cancer accounted for 14.57% (95% uncertainty interval: 13.65–15.28) of total deaths and 8.8% (7.99–9.67) of total DALYs in both sexes globally. ASIR and ASDR were 790.33 (694.43–893.01) and 116.49 (107.28–124.69), respectively. Additionally, females exhibited higher ASIR than males (923.44 versus 673.09), while males exhibited higher ASDR than females (145.69 versus 93.60). This indicates that policymakers should focus on the importance of gender equality in healthcare. Non-melanoma skin cancer exhibited the highest ASIR (74.10) in both sexes, while digestive cancers accounted for 39.29% of all cancer-related deaths, and Asia exhibited the heaviest cancer burden. In females, breast cancer exhibited the highest ASIR (46.40) and ASDR (14.55). In males, tracheal, bronchial, and lung cancer exhibited the highest ASIR (37.85) and ASDR (34.32), highlighting the urgent need for targeted tobacco control measures. Different cancers in various countries exhibit unique characteristics. Therefore, policymakers should formulate specific prevention and control strategies that reflect the cancer in their country. Tobacco was the primary level 2 risk factor for cancer DALYs in males. It accounted for 29.32% (25.32–33.14) of all cancer DALYs. Dietary risks, alcohol consumption, and air pollution accounted for 5.89% (2.01–10.73), 5.48% (4.83–6.11), and 4.30% (2.77–5.95) of male cancer DALYs, respectively. Therefore, policymakers should prioritize smoking regulation and other carcinogenic risks. Cancer is a significant public health concern globally. Understanding the common etiologies of different cancers is essential for developing effective control strategies and targeted interventions.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753667","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}

{"title":"The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study","authors":"Dan-Yun Ruan, Xiao-Li Wei, Fu-Rong Liu, Xi-Chun Hu, Jian Zhang, Dong-Mei Ji, Ding-Zhi Huang, Yan-Qiu Zhao, Hong-Min Pan, Wang-Jun Liao, Kun-Yu Yang, Nong Xu, Xiao-Xiao Lu, Yu-Ling Chen, Wen Zhang, Hui Zhou, Hong-Yun Zhao, Rui-Hua Xu","doi":"10.1186/s13045-024-01644-4","DOIUrl":"https://doi.org/10.1186/s13045-024-01644-4","url":null,"abstract":"There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors. In this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics. From February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n = 55; Phase Ib, n = 48). The median follow-up was 10.1 months (range 0.7–28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments. IBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"84 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753668","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}