Pub Date : 2025-03-07DOI: 10.1186/s13045-025-01681-7
Qiling Bu, Hong-Hu Zhu, Wenming Chen
Immunoglobulin light chain (AL) amyloidosis is an incurable disease caused by the accumulation and sedimentation of unstable free light chains produced by monoclonal plasma cells. The key to treatment is to achieve a deep hematologic remission in order to improve organ function or reverse organ dysfunction. Conventional treatment has not been able to fully meet the treatment needs of patients with AL, while therapies targeting malignant plasma cells or amyloid have potentially improved treatment outcomes. This study provides an overview of the latest reports on targeted therapies for AL amyloidosis from the 2024 ASH Annual Meeting.
免疫球蛋白轻链（AL）淀粉样变性是一种不治之症，由单克隆浆细胞产生的不稳定游离轻链堆积沉淀所致。治疗的关键是实现深度血液学缓解，以改善器官功能或逆转器官功能障碍。传统治疗无法完全满足 AL 患者的治疗需求，而针对恶性浆细胞或淀粉样蛋白的疗法则有可能改善治疗效果。本研究概述了2024年ASH年会上有关AL淀粉样变性靶向疗法的最新报道。
{"title":"Novel targeted therapies for immunoglobulin light chain amyloidosis: latest updates from the 2024 ASH annual meeting","authors":"Qiling Bu, Hong-Hu Zhu, Wenming Chen","doi":"10.1186/s13045-025-01681-7","DOIUrl":"https://doi.org/10.1186/s13045-025-01681-7","url":null,"abstract":"Immunoglobulin light chain (AL) amyloidosis is an incurable disease caused by the accumulation and sedimentation of unstable free light chains produced by monoclonal plasma cells. The key to treatment is to achieve a deep hematologic remission in order to improve organ function or reverse organ dysfunction. Conventional treatment has not been able to fully meet the treatment needs of patients with AL, while therapies targeting malignant plasma cells or amyloid have potentially improved treatment outcomes. This study provides an overview of the latest reports on targeted therapies for AL amyloidosis from the 2024 ASH Annual Meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"33 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569433","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 : 2025-03-07DOI: 10.1186/s13045-025-01680-8
Yahui Ding, Yongping Bai, Tianyang Chen, Sisi Chen, Wanjing Feng, Shuoqian Ma, Quan Zhang
Pancreatic cancer is one of the most malignant cancers, and limited therapeutic options are available. The induction of ferroptosis is considered to be a novel, promising strategy that has potential in cancer treatment, and ferroptosis inducers may be new options for eradicating malignant cancers that are resistant to traditional drugs. The exact mechanism underlying the function of sorcin in the initiation and progression of pancreatic cancer remains unclear. The expression of sorcin in cancer tissues was assessed by analyzing TCGA, GEO and immunohistochemical staining data, and the function of sorcin in the induction of ferroptosis in pancreatic cancer cells was investigated. The mechanism underlying the function of sorcin was revealed through proteomics, co-IP, Ch-IP, and luciferase assays. Natural product screening was subsequently performed to screen for products that interact with sorcin to identify new ferroptosis inducers. We first showed that sorcin expression was positively correlated with the survival and tumor stages of patients with pancreatic cancer, and we revealed that sorcin inhibited ferroptosis through its noncalcium binding function. Furthermore, we discovered that sorcin interacted with PAX5 in the cytoplasm and inhibited PAX5 nuclear translocation, which in turn decreased FBXL12 protein expression and then reduced ALDH1A1 ubiquitination, thus inhibiting ferroptosis. Moreover, an in-house natural product screen revealed that celastrol inhibited the interaction of sorcin and PAX5 by directly binding to the Cys194 residue of the sorcin protein; disruption of the sorcin-PAX5 interaction promoted the nuclear translocation of PAX5, induced the expression of FBXL12, increased the ubiquitylation of ALDH1A1, and eventually induced ferroptosis in pancreatic cancer cells. In this study, we revealed the mechanism of action of sorcin, which is a druggable target for inducing ferroptosis, we identified celastrol as a novel agent that induces ferroptosis, and we showed that disrupting the sorcin-PAX5 interaction is a promising therapeutic strategy for treating pancreatic cancer.
{"title":"Disruption of the sorcin‒PAX5 protein‒protein interaction induces ferroptosis by promoting the FBXL12-mediated ubiquitination of ALDH1A1 in pancreatic cancer","authors":"Yahui Ding, Yongping Bai, Tianyang Chen, Sisi Chen, Wanjing Feng, Shuoqian Ma, Quan Zhang","doi":"10.1186/s13045-025-01680-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01680-8","url":null,"abstract":"Pancreatic cancer is one of the most malignant cancers, and limited therapeutic options are available. The induction of ferroptosis is considered to be a novel, promising strategy that has potential in cancer treatment, and ferroptosis inducers may be new options for eradicating malignant cancers that are resistant to traditional drugs. The exact mechanism underlying the function of sorcin in the initiation and progression of pancreatic cancer remains unclear. The expression of sorcin in cancer tissues was assessed by analyzing TCGA, GEO and immunohistochemical staining data, and the function of sorcin in the induction of ferroptosis in pancreatic cancer cells was investigated. The mechanism underlying the function of sorcin was revealed through proteomics, co-IP, Ch-IP, and luciferase assays. Natural product screening was subsequently performed to screen for products that interact with sorcin to identify new ferroptosis inducers. We first showed that sorcin expression was positively correlated with the survival and tumor stages of patients with pancreatic cancer, and we revealed that sorcin inhibited ferroptosis through its noncalcium binding function. Furthermore, we discovered that sorcin interacted with PAX5 in the cytoplasm and inhibited PAX5 nuclear translocation, which in turn decreased FBXL12 protein expression and then reduced ALDH1A1 ubiquitination, thus inhibiting ferroptosis. Moreover, an in-house natural product screen revealed that celastrol inhibited the interaction of sorcin and PAX5 by directly binding to the Cys194 residue of the sorcin protein; disruption of the sorcin-PAX5 interaction promoted the nuclear translocation of PAX5, induced the expression of FBXL12, increased the ubiquitylation of ALDH1A1, and eventually induced ferroptosis in pancreatic cancer cells. In this study, we revealed the mechanism of action of sorcin, which is a druggable target for inducing ferroptosis, we identified celastrol as a novel agent that induces ferroptosis, and we showed that disrupting the sorcin-PAX5 interaction is a promising therapeutic strategy for treating pancreatic cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569436","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}
Despite the success of immune checkpoint inhibitors (ICIs) in multiple malignant tumors, a significant proportion of patients remain unresponsive to treatment. Radiotherapy (RT) elicits immunogenic antitumor responses but concurrently activates several immune evasion mechanisms. Our earlier research demonstrated the efficacy of YM101, an anti-TGF-β/PD-L1 bispecific antibody, in stroma-rich tumors. Nevertheless, YM101 has demonstrated reduced effectiveness in non-inflamed tumors characterized by poor immune cell infiltration. This study investigated the potential synergy between RT and YM101 in overcoming immunotherapy resistance and mitigating RT-induced pulmonary fibrosis. The antitumor activity and survival outcomes of RT plus YM101 treatment in vivo were explored in several non-inflamed murine tumor models. Furthermore, the inhibition of pulmonary metastases was assessed in a pulmonary metastasis model. The impact of RT on dendritic cell (DC) maturation was quantified by flow cytometry, whereas cytokine and chemokine secretions were measured by ELISA. To comprehensively characterize changes in the tumor microenvironment, we utilized a combination of methods, including flow cytometry, IHC staining, multiplex inmunofluorecence and RNA sequencing. Additionally, we evaluated the impact of YM101 on RT-induced pulmonary fibrosis. RT plus YM101 significantly inhibited tumor growth, prolonged survival and inhibited pulmonary metastases compared with monotherapies in non-inflamed tumors with poor immune infiltration. RT promoted DC maturation in a dose-dependent manner and increased the secretions of multiple proinflammatory cytokines. Mechanistically, RT plus YM101 simultaneously increased the infiltration and activation of intratumoral DCs and tumor-infiltrating lymphocytes and reshaped the tumor microenvironment landscape. Notably, YM101 attenuated both RT-induced peritumoral fibrosis and pulmonary fibrosis. Our findings suggest that RT combined with YM101 enhances antitumor immunity and overcomes resistance in non-inflamed tumors in preclinical models, while simultaneously showing potential in mitigating RT-induced fibrosis. This combination therapy demonstrates promise in overcoming ICI resistance, while potentially sparing normal pulmonary tissue, thereby providing a strong rationale for further clinical investigations.
{"title":"Anti-TGF-β/PD-L1 bispecific antibody synergizes with radiotherapy to enhance antitumor immunity and mitigate radiation-induced pulmonary fibrosis","authors":"Yuze Wu, Yuheng Yan, Yarong Guo, Mengke Niu, Binghan Zhou, Jing Zhang, Pengfei Zhou, Qian Chu, Qi Mei, Ming Yi, Kongming Wu","doi":"10.1186/s13045-025-01678-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01678-2","url":null,"abstract":"Despite the success of immune checkpoint inhibitors (ICIs) in multiple malignant tumors, a significant proportion of patients remain unresponsive to treatment. Radiotherapy (RT) elicits immunogenic antitumor responses but concurrently activates several immune evasion mechanisms. Our earlier research demonstrated the efficacy of YM101, an anti-TGF-β/PD-L1 bispecific antibody, in stroma-rich tumors. Nevertheless, YM101 has demonstrated reduced effectiveness in non-inflamed tumors characterized by poor immune cell infiltration. This study investigated the potential synergy between RT and YM101 in overcoming immunotherapy resistance and mitigating RT-induced pulmonary fibrosis. The antitumor activity and survival outcomes of RT plus YM101 treatment in vivo were explored in several non-inflamed murine tumor models. Furthermore, the inhibition of pulmonary metastases was assessed in a pulmonary metastasis model. The impact of RT on dendritic cell (DC) maturation was quantified by flow cytometry, whereas cytokine and chemokine secretions were measured by ELISA. To comprehensively characterize changes in the tumor microenvironment, we utilized a combination of methods, including flow cytometry, IHC staining, multiplex inmunofluorecence and RNA sequencing. Additionally, we evaluated the impact of YM101 on RT-induced pulmonary fibrosis. RT plus YM101 significantly inhibited tumor growth, prolonged survival and inhibited pulmonary metastases compared with monotherapies in non-inflamed tumors with poor immune infiltration. RT promoted DC maturation in a dose-dependent manner and increased the secretions of multiple proinflammatory cytokines. Mechanistically, RT plus YM101 simultaneously increased the infiltration and activation of intratumoral DCs and tumor-infiltrating lymphocytes and reshaped the tumor microenvironment landscape. Notably, YM101 attenuated both RT-induced peritumoral fibrosis and pulmonary fibrosis. Our findings suggest that RT combined with YM101 enhances antitumor immunity and overcomes resistance in non-inflamed tumors in preclinical models, while simultaneously showing potential in mitigating RT-induced fibrosis. This combination therapy demonstrates promise in overcoming ICI resistance, while potentially sparing normal pulmonary tissue, thereby providing a strong rationale for further clinical investigations.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546215","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 : 2025-03-05DOI: 10.1186/s13045-025-01674-6
Na Li, Jianpeng Sheng, Hong-Hu Zhu
Degrader therapies have garnered significant attention for their innovative approach to targeting and eliminating malignancy-associated proteins, holding promise for improving outcomes for patients with relapsed or refractory (R/R) hematological malignancies, especially in cases of leukemia, non-Hodgkin lymphoma, and multiple myeloma. Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting.
{"title":"Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024","authors":"Na Li, Jianpeng Sheng, Hong-Hu Zhu","doi":"10.1186/s13045-025-01674-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01674-6","url":null,"abstract":"Degrader therapies have garnered significant attention for their innovative approach to targeting and eliminating malignancy-associated proteins, holding promise for improving outcomes for patients with relapsed or refractory (R/R) hematological malignancies, especially in cases of leukemia, non-Hodgkin lymphoma, and multiple myeloma. Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"12 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546214","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 : 2025-03-05DOI: 10.1186/s13045-025-01682-6
Jingyao Lian, Ying Yue, Weina Yu, Yi Zhang
<p><b>Correction: Journal of Hematology & Oncology (2020) 13:151</b></p><p>https://doi.org/10.1186/s13045-020-00986-z</p><p>In the ahead-mentioned sentence in the original article, ‘KLRG1' was incorrectly written as ‘NKG2C’, leading to an inaccurate statement.</p><p>The authors regret this oversight and wish to clarify that the corrected sentence should instead read:</p><p>“It should be noted that, in the process of immunosenescence, the activating receptor expression of natural killer (NK) cell markers NKP30, NKP46, etc., is reduced, while the inhibitory receptor expression of KIR, KLRG1, etc., is increased”.</p><span>Author notes</span><ol><li><p>Jingyao Lian, Ying Yue, and Weina Yu contributed equally to this work</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, Henan, China</p><p>Jingyao Lian, Ying Yue, Weina Yu & Yi Zhang</p></li><li><p>State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450052, Henan, China</p><p>Jingyao Lian, Ying Yue, Weina Yu & Yi Zhang</p></li><li><p>Clinical Laboratory, Henan Medical College Hospital Workers, Zhengzhou, 450000, Henan, China</p><p>Ying Yue</p></li></ol><span>Authors</span><ol><li><span>Jingyao Lian</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ying Yue</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Weina Yu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yi Zhang</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 Yi Zhang.</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/s13045-020-00986-z</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyri
{"title":"Correction: Immunosenescence: a key player in cancer development","authors":"Jingyao Lian, Ying Yue, Weina Yu, Yi Zhang","doi":"10.1186/s13045-025-01682-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01682-6","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2020) 13:151</b></p><p>https://doi.org/10.1186/s13045-020-00986-z</p><p>In the ahead-mentioned sentence in the original article, ‘KLRG1' was incorrectly written as ‘NKG2C’, leading to an inaccurate statement.</p><p>The authors regret this oversight and wish to clarify that the corrected sentence should instead read:</p><p>“It should be noted that, in the process of immunosenescence, the activating receptor expression of natural killer (NK) cell markers NKP30, NKP46, etc., is reduced, while the inhibitory receptor expression of KIR, KLRG1, etc., is increased”.</p><span>Author notes</span><ol><li><p>Jingyao Lian, Ying Yue, and Weina Yu contributed equally to this work</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, Henan, China</p><p>Jingyao Lian, Ying Yue, Weina Yu & Yi Zhang</p></li><li><p>State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450052, Henan, China</p><p>Jingyao Lian, Ying Yue, Weina Yu & Yi Zhang</p></li><li><p>Clinical Laboratory, Henan Medical College Hospital Workers, Zhengzhou, 450000, Henan, China</p><p>Ying Yue</p></li></ol><span>Authors</span><ol><li><span>Jingyao Lian</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ying Yue</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Weina Yu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yi Zhang</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 Yi Zhang.</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/s13045-020-00986-z</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyri","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"40 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546467","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}
B-cell maturation antigen (BCMA) is currently the most extensively explored target for multiple myeloma (MM). BCMA-targeted therapies such as antibody-drug conjugate (ADC), bispecific antibodies (BsAbs), chimeric antigen receptor T(CAR-T) cell have shown promising therapeutic prospects in MM. We have summarized the latest reports on the three types of drugs for MM at the 2024 ASH Annual Meeting.
{"title":"BCMA-targeted therapies for multiple myeloma: latest updates from 2024 ASH annual meeting","authors":"Huijian Zheng, Huajian Xian, Wenjie Zhang, Chaoqun Lu, Renyao Pan, Han Liu, Zhenshu Xu","doi":"10.1186/s13045-025-01675-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01675-5","url":null,"abstract":"B-cell maturation antigen (BCMA) is currently the most extensively explored target for multiple myeloma (MM). BCMA-targeted therapies such as antibody-drug conjugate (ADC), bispecific antibodies (BsAbs), chimeric antigen receptor T(CAR-T) cell have shown promising therapeutic prospects in MM. We have summarized the latest reports on the three types of drugs for MM at the 2024 ASH Annual Meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528212","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 : 2025-03-01DOI: 10.1186/s13045-025-01677-3
Ran Kong, Bingyu Liu, Hua Wang, Tiange Lu, Xiangxiang Zhou
Natural killer cells, integral to the innate immune response, exhibit the inherent capacity to identify and eliminate cancer cells without prior exposure, positioning them as prime candidates for immunotherapeutic strategies. Chimeric antigen receptor-engineered natural killer (CAR-NK) cells obviate the requirement for human leukocyte antigen compatibility, simplifying personalized schedules and facilitating the manufacture of off-the-shelf products. In addition, CAR-NK cell therapy possesses lower risk of cytokine release syndrome and neurotoxicity, benefitting patients with higher security. Nevertheless, CAR-NK cell therapy is also confronted with challenges, including but not limited to short lifespan and restrictions from tumor microenvironment. Here, we summarized the latest advancements in the preclinical investigations and clinical trials of CAR-NK cell therapy from the 2024 ASH Annual Meeting.
{"title":"CAR-NK cell therapy: latest updates from the 2024 ASH annual meeting","authors":"Ran Kong, Bingyu Liu, Hua Wang, Tiange Lu, Xiangxiang Zhou","doi":"10.1186/s13045-025-01677-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01677-3","url":null,"abstract":"Natural killer cells, integral to the innate immune response, exhibit the inherent capacity to identify and eliminate cancer cells without prior exposure, positioning them as prime candidates for immunotherapeutic strategies. Chimeric antigen receptor-engineered natural killer (CAR-NK) cells obviate the requirement for human leukocyte antigen compatibility, simplifying personalized schedules and facilitating the manufacture of off-the-shelf products. In addition, CAR-NK cell therapy possesses lower risk of cytokine release syndrome and neurotoxicity, benefitting patients with higher security. Nevertheless, CAR-NK cell therapy is also confronted with challenges, including but not limited to short lifespan and restrictions from tumor microenvironment. Here, we summarized the latest advancements in the preclinical investigations and clinical trials of CAR-NK cell therapy from the 2024 ASH Annual Meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"34 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528246","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 : 2025-02-24DOI: 10.1186/s13045-025-01672-8
Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li
<p><b>Correction: Journal of Hematology & Oncology (2017) 10:68 </b><b>https://doi.org/10.1186/s13045-017-0437-8</b></p><p>The authors wish to note the following:</p><p>In Supplemental Figure 1, the flow cytometry data that represent the transfection efficiencies of Meso.28z T cells on Day 12 and Day 15 were mistakenly duplicated. Both panels display a percentage of 34.9%, but upon reviewing our raw data, we found that the correct transfection efficiency for Day 15 should be 34.4%, not 34.9%. This discrepancy was caused by an error in copying and pasting during data preparation.</p><p>We confirm that this correction does not impact the overall conclusions or interpretation of the results presented in the article. To address this mistake, we kindly request the opportunity to replace the original Supplemental Figure 1 with a revised figure that accurately reflects the values. The original and revised Supplementary Figure 1 can be viewed via this Correction article.</p><span>Author notes</span><ol><li><p>Le Qin and Yunxin Lai are equal contributors.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao & Peng Li</p></li><li><p>Department of Hematology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China</p><p>Jianyu Weng, Peilong Lai & Xin Du</p></li><li><p>InVivo Biomedicine Co. Ltd, Guangzhou, 510000, China</p><p>Qiubin Liang</p></li><li><p>Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China</p><p>Yangqiu Li</p></li><li><p>Guangdong Lung Cancer Institute, Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China</p><p>Xuchao Zhang & Yilong Wu</p></li><li><p>Wellcome Trust Sanger Institute, Hinxton, Cambridge, England, CB10 1HH, UK</p><p>Pentao Liu</p></li></ol><span>Authors</span><ol><li><span>Le Qin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Sch
{"title":"Correction: Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells","authors":"Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li","doi":"10.1186/s13045-025-01672-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01672-8","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2017) 10:68 </b><b>https://doi.org/10.1186/s13045-017-0437-8</b></p><p>The authors wish to note the following:</p><p>In Supplemental Figure 1, the flow cytometry data that represent the transfection efficiencies of Meso.28z T cells on Day 12 and Day 15 were mistakenly duplicated. Both panels display a percentage of 34.9%, but upon reviewing our raw data, we found that the correct transfection efficiency for Day 15 should be 34.4%, not 34.9%. This discrepancy was caused by an error in copying and pasting during data preparation.</p><p>We confirm that this correction does not impact the overall conclusions or interpretation of the results presented in the article. To address this mistake, we kindly request the opportunity to replace the original Supplemental Figure 1 with a revised figure that accurately reflects the values. The original and revised Supplementary Figure 1 can be viewed via this Correction article.</p><span>Author notes</span><ol><li><p>Le Qin and Yunxin Lai are equal contributors.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao & Peng Li</p></li><li><p>Department of Hematology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China</p><p>Jianyu Weng, Peilong Lai & Xin Du</p></li><li><p>InVivo Biomedicine Co. Ltd, Guangzhou, 510000, China</p><p>Qiubin Liang</p></li><li><p>Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China</p><p>Yangqiu Li</p></li><li><p>Guangdong Lung Cancer Institute, Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China</p><p>Xuchao Zhang & Yilong Wu</p></li><li><p>Wellcome Trust Sanger Institute, Hinxton, Cambridge, England, CB10 1HH, UK</p><p>Pentao Liu</p></li></ol><span>Authors</span><ol><li><span>Le Qin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Sch","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"49 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485821","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}
In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing a particularly promising avenue of investigation. The identification of ncRNA-encoded peptides in human cancers is increasing. These peptides regulate cancer progression through multiple molecular mechanisms. Here, we delineate the patterns of diverse ncRNA-encoded peptides and provide a synopsis of the methodologies employed for the identification of ncRNAs that possess the capacity to encode these peptides. Furthermore, we discuss the impacts of ncRNA-encoded peptides on the biological behavior of cancer cells and the underlying molecular mechanisms. In conclusion, we describe the prospects of ncRNA-encoded peptides in cancer and the challenges that need to be overcome.
{"title":"Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential","authors":"Shiming Tan, Wenjuan Yang, Zongyao Ren, Qiu Peng, Xuemeng Xu, Xianjie Jiang, Zhu Wu, Linda Oyang, Xia Luo, Jinguan Lin, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Yaqian Han, Qianjin Liao, Yujuan Zhou","doi":"10.1186/s13045-025-01671-9","DOIUrl":"https://doi.org/10.1186/s13045-025-01671-9","url":null,"abstract":"In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing a particularly promising avenue of investigation. The identification of ncRNA-encoded peptides in human cancers is increasing. These peptides regulate cancer progression through multiple molecular mechanisms. Here, we delineate the patterns of diverse ncRNA-encoded peptides and provide a synopsis of the methodologies employed for the identification of ncRNAs that possess the capacity to encode these peptides. Furthermore, we discuss the impacts of ncRNA-encoded peptides on the biological behavior of cancer cells and the underlying molecular mechanisms. In conclusion, we describe the prospects of ncRNA-encoded peptides in cancer and the challenges that need to be overcome.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"64 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451445","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 : 2025-02-18DOI: 10.1186/s13045-025-01664-8
Zihai Li, John Wrangle, Kai He, Jonathan Sprent, Mark P. Rubinstein
<p>In April 2024, the FDA approved the interleukin (IL)−15 superagonist, N-803 (Anktiva, nogapendekin alfa inbakicept-pmln), for the treatment of bladder cancer [1]. This is the first cytokine in over 30 years to receive FDA approval for the treatment of cancer, and the culmination of years of preclinical and clinical studies involving both academic- and industry- driven research.</p><p>To understand the steps leading to this landmark approval, it is helpful to review some key historical events (Fig. 1). Notably, the first cytokines FDA approved for the treatment of cancer were interferon (type 1) (1986, hairy cell leukemia) and IL-2 (1992, renal cell carcinoma) [2]. Within a few years of their initial approvals, both cytokines would also receive other FDA approvals including for the treatment of metastatic melanoma. While both cytokines have broad immune stimulatory activities, IL-2 is unique in that it is also a powerful lymphocyte growth factor [3,4,5,6]. These qualities led to the evaluation and use of IL-2 with many other experimental immunotherapies including adoptive cell therapy. Notably, the adoptive transfer of tumor infiltrating lymphocytes (TIL) in combination with IL-2 first showed efficacy in human patients in the late 1980s [7]. After decades of work, in February 2024, TIL (lifileucel) in combination with IL-2 received FDA approval for the treatment of melanoma [8], which is the first approved adoptive cell therapy using lymphocytes for the treatment of a solid tumor.</p><figure><figcaption><b data-test="figure-caption-text">Fig. 1</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png?as=webp" type="image/webp"/><img alt="figure 1" aria-describedby="Fig1" height="170" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png" width="685"/></picture><p>Timeline of key events related to the discovery and development of IL-15 and BCG as therapeutics</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-chevron-right-small" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></figure><p>Despite its established efficacy, IL-2 has a short half-life, and at approved doses, IL-2 can induce life threatening toxicities [9]. This side effect profile likely severely curtailed subsequent clinical development. Thus, high dose IL-2 as a monotherapy was FDA approved for renal cell carcinoma and metastatic melanoma, clinical development for other indications halted despite evidence of efficacy in other cancers [10]. Thus began the effort to develop alternatives with a similar mechanism of action.</p><p>The discovery of IL-15 in 1994 was the first step in the development of a promising alternative to IL-2 [4,5,6, 11,12,13]. Like IL-2, IL-15 is a powerful
{"title":"IL-15: from discovery to FDA approval","authors":"Zihai Li, John Wrangle, Kai He, Jonathan Sprent, Mark P. Rubinstein","doi":"10.1186/s13045-025-01664-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01664-8","url":null,"abstract":"<p>In April 2024, the FDA approved the interleukin (IL)−15 superagonist, N-803 (Anktiva, nogapendekin alfa inbakicept-pmln), for the treatment of bladder cancer [1]. This is the first cytokine in over 30 years to receive FDA approval for the treatment of cancer, and the culmination of years of preclinical and clinical studies involving both academic- and industry- driven research.</p><p>To understand the steps leading to this landmark approval, it is helpful to review some key historical events (Fig. 1). Notably, the first cytokines FDA approved for the treatment of cancer were interferon (type 1) (1986, hairy cell leukemia) and IL-2 (1992, renal cell carcinoma) [2]. Within a few years of their initial approvals, both cytokines would also receive other FDA approvals including for the treatment of metastatic melanoma. While both cytokines have broad immune stimulatory activities, IL-2 is unique in that it is also a powerful lymphocyte growth factor [3,4,5,6]. These qualities led to the evaluation and use of IL-2 with many other experimental immunotherapies including adoptive cell therapy. Notably, the adoptive transfer of tumor infiltrating lymphocytes (TIL) in combination with IL-2 first showed efficacy in human patients in the late 1980s [7]. After decades of work, in February 2024, TIL (lifileucel) in combination with IL-2 received FDA approval for the treatment of melanoma [8], which is the first approved adoptive cell therapy using lymphocytes for the treatment of a solid tumor.</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"170\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png\" width=\"685\"/></picture><p>Timeline of key events related to the discovery and development of IL-15 and BCG as therapeutics</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Despite its established efficacy, IL-2 has a short half-life, and at approved doses, IL-2 can induce life threatening toxicities [9]. This side effect profile likely severely curtailed subsequent clinical development. Thus, high dose IL-2 as a monotherapy was FDA approved for renal cell carcinoma and metastatic melanoma, clinical development for other indications halted despite evidence of efficacy in other cancers [10]. Thus began the effort to develop alternatives with a similar mechanism of action.</p><p>The discovery of IL-15 in 1994 was the first step in the development of a promising alternative to IL-2 [4,5,6, 11,12,13]. Like IL-2, IL-15 is a powerful ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"12 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434910","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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