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Lipid-based nanosystems: the next generation of cancer immune therapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-07-19 Ziyun Cheng, Seth-Frerich Fobian, Elena Gurrieri, Mohamadreza Amin, Vito Giuseppe D’Agostino, Mojtaba Falahati, Sara Zalba, Reno Debets, María J. Garrido, Mesha Saeed, Ann L. B. Seynhaeve, Hayri E. Balcioglu, Timo L. M. ten Hagen
Immunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical
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Menin inhibitors for acute myeloid leukemia: latest updates from the 2023 ASH Annual Meeting J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-07-19 Zhuo-Yu An, Xiao-Hui Zhang
Recent developments in menin inhibitors for relapsed or refractory acute myeloid leukemia (AML) were highlighted at the 2023 ASH Annual Meeting. Notably, revumenib showed promising efficacy, achieving a 100% ORR when combined with decitabine/cedazuridine and venetoclax. These findings underscore the potential of menin inhibitors in transforming AML treatment, particularly in genetically defined subgroups
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Mature B, T and NK-cell, plasma cell and histiocytic/dendritic cell neoplasms: classification according to the World Health Organization and International Consensus Classification J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-07-08 Judith A. Ferry, Brian Hill, Eric D. Hsi
In 2022, two updated classification systems for lymphoid neoplasms were published by the World Health Organization (WHO Classification of Haematolymphoid Tumours, 5th edition, referred to hereafter as WHO-HAEM5) and the International Consensus Conference (ICC) (Alaggio et al. in Leukemia 36(7):1720–1748, 2022; Campo et al. in Blood 140(11):1229–1253, 2022). Both classifications were conceived by both
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Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-27 Swati Naik, Ying Li, Aimee C. Talleur, Subodh Selukar, Emily Ashcraft, Cheng Cheng, Renee M. Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Ali Y. Suliman, Rebecca Epperly, Esther A. Obeng, M. Paulina Velasquez, Deanna Langfitt, Sarah Schell, Jean-Yves Métais, Paula Y. Arnold, Diego R. Hijano, Gabriela Maron, Thomas E. Merchant, Salem Akel, Wing Leung, Stephen Gottschalk, Brandon
Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might
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Advances in CAR-T-cell therapy in T-cell malignancies J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-24 Rubing Zheng, Xiaojian Zhu, Yi Xiao
Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress
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Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-24 Yingjie Zhang, Xinyue Liang, Weiling Xu, Xingcheng Yi, Rui Hu, Xintian Ma, Yurong Yan, Nan Zhang, Jingxuan Wang, Xiaoxiao Sun, Yufeng Zhu, Mengru Tian, Maozhuo Lan, Mengtuan Long, Yun Dai, Fengyan Jin
It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles
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Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-18 Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang
Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named “IEsohunter”) for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective
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Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-18 Pan Song, Zirui Gao, Yige Bao, Li Chen, Yuhe Huang, Yanyan Liu, Qiang Dong, Xiawei Wei
The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin
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Remodeling of anti-tumor immunity with antibodies targeting a p53 mutant J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-18 Dafei Chai, Junhao Wang, Chunmei Fan, Jing-Ming Lim, Xu Wang, Praveen Neeli, Xinfang Yu, Ken H. Young, Yong Li
p53, the most frequently mutated gene in cancer, lacks effective targeted drugs. We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess
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Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-11 Belén Toledo, Linrui Zhu Chen, María Paniagua-Sancho, Juan Antonio Marchal, Macarena Perán, Elisa Giovannetti
Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles in tumour growth, angiogenesis, immune regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 and M2 subtypes based on their differentiation and activities
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Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-09 Tobias Ronny Haage, Emmanouil Charakopoulos, Vikas Bhuria, Conny K. Baldauf, Mark Korthals, Juliane Handschuh, Peter Müller, Juan Li, Kunjan Harit, Gopala Nishanth, Stephanie Frey, Martin Böttcher, Klaus-Dieter Fischer, Jan Dudeck, Anne Dudeck, Daniel B. Lipka, Burkhart Schraven, Anthony R. Green, Andreas J. Müller, Dimitrios Mougiakakos, Thomas Fischer
Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type
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Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-06 Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter Forsberg, Douglas Sborov, Larry D. Anderson Jr, Joseph P. McGuirk, Charlotte Wagner, Alex Lieberman-Cribbin, Adriana Rossi, Ciara L. Freeman, Frederick L. Locke, Shambavi Richard, Jack Khouri, Yi Lin, Krina
Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or
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Ferroptosis: principles and significance in health and disease J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-06 Fangquan Chen, Rui Kang, Daolin Tang, Jiao Liu
Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across
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Current and future immunotherapeutic approaches in pancreatic cancer treatment J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-04 Pooya Farhangnia, Hossein Khorramdelazad, Hamid Nickho, Ali-Akbar Delbandi
Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type of tumor have remained grim for a long time. Currently, it is extremely challenging to prevent or detect it early enough for effective treatment because patients rarely exhibit symptoms and there are no reliable indicators for detection. Most patients have advanced or spreading
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Targeting FGFR for cancer therapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-03 Pei Zhang, Lin Yue, QingQing Leng, Chen Chang, Cailing Gan, Tinghong Ye, Dan Cao
The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development
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Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-06-01 Esther Wei Yin Chang, Ya Hwee Tan, Jason Yongsheng Chan
Peripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage
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Advances in targeting histone deacetylase for treatment of solid tumors J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-31 Mu-Qi Shi, Ying Xu, Xin Fu, De-Si Pan, Xian-Ping Lu, Yi Xiao, Yi-Zhou Jiang
Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments
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Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-23 Yiye Zhong, Huangying Le, Xue Zhang, Yao Dai, Fang Guo, Xiaojuan Ran, Guohong Hu, Qi Xie, Dawei Wang, Yujia Cai
Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication
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Generation of sarconoids from angiosarcoma patients as a systematic-based rational approach to treatment J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-20 Da Jung Jung, Jae Hee Byeon, Young Chul Kim, Woo Shik Jeong, Jong-Woo Choi, Gi Seok Jeong
Angiosarcoma is a rare subtype of malignant neoplasm originating from vascular or lymphatic endothelial cells; its low incidence has posed significant challenges for comprehensive investigations into its pathogenic mechanisms and the development of innovative treatment modalities through in vitro and in vivo models. Recent endeavors spearheaded by patient-partnered research initiatives have aimed to
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PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-20 Fei Zhou, Feng Du, Ziyan Wang, Mengxing Xue, Depei Wu, Suning Chen, Xuefeng He
Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection
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Critical role of the gut microbiota in immune responses and cancer immunotherapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-14 Zehua Li, Weixi Xiong, Zhu Liang, Jinyu Wang, Ziyi Zeng, Damian Kołat, Xi Li, Dong Zhou, Xuewen Xu, Linyong Zhao
The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this
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Inotuzumab ozogamicin for the treatment of adult acute lymphoblastic leukemia: past progress, current research and future directions J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-11 Nicholas J. Short, Elias Jabbour, Nitin Jain, Hagop Kantarjian
Inotuzumab ozogamicin (INO) is an anti-CD22 antibody-drug conjugate that was first evaluated in B-cell lymphomas but was subsequently shown to be highly effective in acute lymphoblastic leukemia (ALL). INO improved response rates and survival in a randomized study in adults with relapsed/refractory B-cell ALL, leading to its regulatory approval in the United States in 2017. While the formal approval
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Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-08 Hao Lin, Chaxian Liu, Ankang Hu, Duanwu Zhang, Hui Yang, Ying Mao
Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and
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Small molecule inhibitors targeting m6A regulators J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-06 Guotai Feng, Yongya Wu, Yuan Hu, Wen Shuai, Xiao Yang, Yong Li, Liang Ouyang, Guan Wang
As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis,
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Off-the-shelf CAR-T cell therapies for relapsed or refractory B-cell malignancies: latest update from ASH 2023 annual meeting J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-06 Yun Kang, Chenggong Li, Heng Mei
Currently, many off-the-shelf chimeric antigen receptor (CAR)-T cell products are under investigation for the treatment of relapsed or refractory (R/R) B-cell neoplasms. Compared with autologous CAR-T cell therapy, off-the-shelf universal CAR-T cell therapies have many potential benefits, such as immediate accessibility for patients, stable quality due to industrialized manufacturing and additional
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Identifying long-term survivors and those at higher or lower risk of relapse among patients with cytogenetically normal acute myeloid leukemia using a high-dimensional mixture cure model J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-03 Kellie J. Archer, Han Fu, Krzysztof Mrózek, Deedra Nicolet, Alice S. Mims, Geoffrey L. Uy, Wendy Stock, John C. Byrd, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H. Metzeler, Tobias Herold, Ann-Kathrin Eisfeld
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials
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ChatGPT’s ability to generate realistic experimental images poses a new challenge to academic integrity J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-05-01 Lingxuan Zhu, Yancheng Lai, Weiming Mou, Haoran Zhang, Anqi Lin, Chang Qi, Tao Yang, Liling Xu, Jian Zhang, Peng Luo
The rapid advancements in large language models (LLMs) such as ChatGPT have raised concerns about their potential impact on academic integrity. While initial concerns focused on ChatGPT’s writing capabilities, recent updates have integrated DALL-E 3’s image generation features, extending the risks to visual evidence in biomedical research. Our tests revealed ChatGPT’s nearly barrier-free image generation
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Germline biallelic BRCA2 pathogenic variants and medulloblastoma: an international cohort study J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-29 Svenja Kastellan, Reinhard Kalb, Bia Sajjad, Lisa J. McReynolds, Neelam Giri, David Samuel, Till Milde, Miriam Elbracht, Susanne Holzhauer, Marena R. Niewisch, Christian P. Kratz
Constitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemia-BRCA signaling pathway, which repairs DNA interstrand crosslinks, represent risk factors for common cancers, including breast, ovarian, pancreatic and prostate cancer. A high cancer risk is also a main clinical feature in patients with Fanconi anemia (FA), a rare condition characterized by bone
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Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-29 Ke-Yu Shen, Ying Zhu, Sun-Zhe Xie, Lun-Xiu Qin
Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs have been the major trend in this area. Recently, dual immune checkpoint blockade with durvalumab plus
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A higher CD34 + cell dose correlates with better event-free survival after KIR-ligand mismatched cord blood transplantation for childhood acute myeloid leukemia J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-29 Hisashi Ishida, Yuta Kawahara, Daisuke Tomizawa, Yasuhiro Okamoto, Asahito Hama, Yuko Cho, Katsuyoshi Koh, Yuhki Koga, Nao Yoshida, Maho Sato, Kiminori Terui, Naoyuki Miyagawa, Akihiro Watanabe, Junko Takita, Ryoji Kobayashi, Masaki Yamamoto, Kenichiro Watanabe, Keiko Okada, Koji Kato, Kimikazu Matsumoto, Moeko Hino, Ken Tabuchi, Hirotoshi Sakaguchi
Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society
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Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-24 Jie Xu, Bai-Yan Wang, Shan-He Yu, Shi-Jun Chen, Shuang-Shuang Yang, Rui Liu, Li-Juan Chen, Jian Hou, Zhu Chen, Wan-Hong Zhao, Ai-Li He, Jian-Qing Mi, Sai-Juan Chen
The autologous anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes
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Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-23 Shimeng Zhou, Junlan Liu, Andi Wan, Yi Zhang, Xiaowei Qi
Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action of various physical, chemical and biological factors. The exploration of tumorigenesis mechanism is crucial for early prevention and treatment of tumors. Epigenetic modification is a common and important modification in cells, including DNA methylation, histone modification, non-coding RNA modification
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Conventional and novel [18F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-23 Doris Leithner, Jessica R. Flynn, Sean M. Devlin, Audrey Mauguen, Teng Fei, Shang Zeng, Junting Zheng, Brandon S. Imber, Harper Hubbeling, Marius E. Mayerhoefer, Akshay Bedmutha, Efrat Luttwak, Magdalena Corona, Parastoo B. Dahi, Alejandro Luna de Abia, Ivan Landego, Richard J. Lin, M. Lia Palomba, Michael Scordo, Jae H. Park, Ana Alarcon Tomas, Gilles Salles, Daniel Lafontaine, Laure Michaud, Gunjan
Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years)
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Heterodimerization of T cell engaging bispecific antibodies to enhance specificity against pancreatic ductal adenocarcinoma J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-23 Alan W Long, Hong Xu, Brian H Santich, Hongfen Guo, Sayed Shahabuddin Hoseini, Elisa de Stanchina, Nai-Kong V Cheung
EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal T cells to these antigens on pancreatic tumors. EGFR and HER2 T-BsAbs were constructed using the 2 + 2 IgG-[L]-scFv T-BsAbs format bearing two anti-CD3 scFvs attached
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Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-22 Guido Ghilardi, Luca Paruzzo, Vrutti Patel, Jakub Svoboda, Emeline R. Chong, Eugenio Fardella, Elise A. Chong, Giulia Gabrielli, Sunita D. Nasta, Daniel J. Landsburg, Jordan Carter, Raymone Pajarillo, Stefan K. Barta, Griffin White, Elizabeth Weber, Ellen Napier, David L. Porter, Alfred L. Garfall, Stephen J. Schuster, Marco Ruella
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB
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Chemo-free treatment of adult patients with Ph-positive acute lymphoblastic leukemia: latest updates from the 2023 ASH annual meeting J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-16 Ting Shi, Hong-Hu Zhu
The chemo-free concept represents a new direction for managing adult patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL). The tyrosine kinase inhibitors (TKIs), blinatumomab and venetoclax serve as the backbone of chemo-free regimens; several prospective studies involving these drugs have demonstrated high remission rates and promising, albeit short, survival outcomes. This review summarizes
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Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-08 Xinxin Wang, Canrong Lu, Bo Wei, Shuo Li, Ziyu Li, Yingwei Xue, Yingjiang Ye, Zhongtao Zhang, Yihong Sun, Han Liang, Kai Li, Linghua Zhu, Zhichao Zheng, Yanbing Zhou, Yulong He, Fei Li, Xin Wang, Pin Liang, Hua Huang, Guoli Li, Xian Shen, Jiafu Ji, Yun Tang, Zekuan Xu, Lin Chen
Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from
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Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-04-02 Qiang Lu, Dongquan Kou, Shenghan Lou, Milad Ashrafizadeh, Amir Reza Aref, Israel Canadas, Yu Tian, Xiaojia Niu, Yuzhuo Wang, Pedram Torabian, Lingzhi Wang, Gautam Sethi, Vinay Tergaonkar, Franklin Tay, Zhennan Yuan, Peng Han
Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME
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Identification of SARS-CoV-2-specific T cell and its receptor J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-27 Qian Zhang, Qing Liang, Rui Zhang, Nan Wang, Xu Xiao, Jiahao Shao, Kejia Wang
The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally
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Targeted protein degradation in hematologic malignancies: latest updates from the 2023 ASH annual meeting J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-22 Guangcai Zhong, Ran Kong, Shi Feng, Cong Wang, Qingbo Hao, Weilin Xie, Xiangxiang Zhou
Protein degraders, emerging as a novel class of therapeutic agents, have gained widespread attention due to their advantages. They have several advantages over traditional small molecule inhibitors, including high target selectivity and ability to target “undruggable” targets and overcome inhibitor drug resistance. Tremendous research and development efforts and massive investment have resulted in
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Targeting inflammation as cancer therapy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-22 Manni Wang, Siyuan Chen, Xuemei He, Yong Yuan, Xiawei Wei
Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to
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Decoding the glycoproteome: a new frontier for biomarker discovery in cancer J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-22 Kai He, Maryam Baniasad, Hyunwoo Kwon, Tomislav Caval, Gege Xu, Carlito Lebrilla, Daniel W. Hommes, Carolyn Bertozzi
Cancer early detection and treatment response prediction continue to pose significant challenges. Cancer liquid biopsies focusing on detecting circulating tumor cells (CTCs) and DNA (ctDNA) have shown enormous potential due to their non-invasive nature and the implications in precision cancer management. Recently, liquid biopsy has been further expanded to profile glycoproteins, which are the products
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Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-15 Fahan Ma, Yan Li, Chan Xiang, Bing Wang, Jie Lv, Jinzhi Wei, Zhaoyu Qin, Yan Pu, Kai Li, Haohua Teng, Subei Tan, Jinwen Feng, Zhanxian Shang, Yunzhi Wang, Sha Tian, Changsheng Du, Yuchen Han, Chen Ding
Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive
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Optical nanomaterial-based detection of biomarkers in liquid biopsy J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-03-14 Young Jun Kim, Won-Yeop Rho, Seung-min Park, Bong-Hyun Jun
Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical
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FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-02-24 Zeda Zhao, Juliang Qin, Ying Qian, Chenshen Huang, Xiaohong Liu, Ning Wang, Liqin Li, Yuqing Chao, Binghe Tan, Na Zhang, Min Qian, Dali Li, Mingyao Liu, Bing Du
Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated
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IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-02-09 Astrid Van den Eynde, Laura Gehrcken, Tias Verhezen, Ho Wa Lau, Christophe Hermans, Hilde Lambrechts, Tal Flieswasser, Delphine Quatannens, Gils Roex, Karen Zwaenepoel, Elly Marcq, Philippe Joye, Edgar Cardenas De La Hoz, Christophe Deben, Alessia Gasparini, Pierre Montay-Gruel, Maxim Le Compte, Eva Lion, Filip Lardon, Steven Van Laere, Vasiliki Siozopoulou, Diana Campillo-Davo, Jorrit De Waele, Patrick
It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue
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METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-02-01 Meilin Xue, Lei Dong, Honghai Zhang, Yangchan Li, Kangqiang Qiu, Zhicong Zhao, Min Gao, Li Han, Anthony K. N. Chan, Wei Li, Keith Leung, Kitty Wang, Sheela Pangeni Pokharel, Ying Qing, Wei Liu, Xueer Wang, Lili Ren, Hongjie Bi, Lu Yang, Chao Shen, Zhenhua Chen, Laleh Melstrom, Hongzhi Li, Nikolai Timchenko, Xiaolan Deng, Wendong Huang, Steven T. Rosen, Jingyan Tian, Lin Xu, Jiajie Diao, Chun-Wei Chen
While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N6-methyladenosine (m6A) methyltransferase, in HCC development/maintenance, CSC stemness
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Metabolic reprogramming in the tumor microenvironment of liver cancer J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-31 Jian Lin, Dongning Rao, Mao Zhang, Qiang Gao
The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements. Overwhelming evidence has illustrated that dysregulated cellular metabolism can, in turn, promote anabolic growth and tumor propagation in a hostile microenvironment. In addition to supporting continuous tumor growth and survival, disrupted
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cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-17 Hongying Zhang, Yongliang Liu, Jieya Liu, Jinzhu Chen, Jiao Wang, Hui Hua, Yangfu Jiang
Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has
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Vaccines: a promising therapy for myelodysplastic syndrome J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-08 Kriti Gera, Anjali Chauhan, Paul Castillo, Maryam Rahman, Akash Mathavan, Akshay Mathavan, Elizabeth Oganda-Rivas, Leighton Elliott, John R. Wingard, Elias J. Sayour
Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with
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The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-08 Lawrence W. Liu, Mei Wang, Nikhil Grandhi, Mark A. Schroeder, Theodore Thomas, Kristin Vargo, Feng Gao, Kristen M. Sanfilippo, Su-Hsin Chang
Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association
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Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-07 Claire Lacan, Jérôme Lambert, Edouard Forcade, Marie Robin, Patrice Chevallier, Sandrine Loron, Claude-Éric Bulabois, Corentin Orvain, Patrice Ceballos, Etienne Daguindau, Amandine Charbonnier, Yves Chalandon, Marc Bernard, Célestine Simand, Marie-Thérèse Rubio, Pascal Turlure, Johan Maertens, Anne Huynh, Michael Loschi, Jacques-Olivier Bay, Gaëlle Guillerm, Mustafa Alani, Cristina Castilla-Llorente
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant
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The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors J. Hematol. Oncol. (IF 29.5) Pub Date : 2024-01-04 Qing Wei, Peijing Li, Teng Yang, Jiayu Zhu, Lu Sun, Ziwen Zhang, Lu Wang, Xuefei Tian, Jiahui Chen, Can Hu, Junli Xue, Letao Ma, Takaya Shimura, Jianmin Fang, Jieer Ying, Peng Guo, Xiangdong Cheng
Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless
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Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-18 Le-Wei Zheng, Cui-Cui Liu, Ke-Da Yu
Liquid–liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecular condensate (BMC) formation via dynamic aggregation. LLPS changes individual molecules into membrane-free, droplet-like BMCs with specific functions, which coordinate various cellular activities. The formation and regulation of LLPS are closely associated
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Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-16 Julie M. Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad Qureishi, Brian K. Link, Melissa H. Cessna, Paul M. Barr, Brad S. Kahl, Matthew S. Mckinney, Nadia Khan, Ranjana H. Advani, Peter Martin, Andre H. Goy, Tycel J. Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R. Flowers, Caron A. Jacobson, Sonali M. Smith
Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for
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Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-16 Dairan Zhou, Zhenyu Gong, Dejun Wu, Chao Ma, Lijun Hou, Xiaomin Niu, Tao Xu
Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor–brain
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Multiscale protein networks systematically identify aberrant protein interactions and oncogenic regulators in seven cancer types J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-15 Won-Min Song, Abdulkadir Elmas, Richard Farias, Peng Xu, Xianxiao Zhou, Benjamin Hopkins, Kuan-lin Huang, Bin Zhang
Global proteomic data generated by advanced mass spectrometry (MS) technologies can help bridge the gap between genome/transcriptome and functions and hold great potential in elucidating unbiased functional models of pro-tumorigenic pathways. To this end, we collected the high-throughput, whole-genome MS data and conducted integrative proteomic network analyses of 687 cases across 7 cancer types including
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Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2 J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-14 Sara Pusceddu, Francesca Corti, Natalie Prinzi, Federico Nichetti, Silva Ljevar, Adele Busico, Tommaso Cascella, Rita Leporati, Simone Oldani, Chiara Carlotta Pircher, Jorgelina Coppa, Veronica Resi, Massimo Milione, Marco Maccauro, Rosalba Miceli, Elena Tamborini, Federica Perrone, Carlo Spreafico, Monica Niger, Federica Morano, Filippo Pietrantonio, Ettore Seregni, Luigi Mariani, Vincenzo Mazzaferro
In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin
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Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-12 Alfonso López de Sá, Cristina Díaz-Tejeiro, Elisa Poyatos-Racionero, Cristina Nieto-Jiménez, Lucía Paniagua-Herranz, Adrián Sanvicente, Emiliano Calvo, Pedro Pérez-Segura, Víctor Moreno, Francisco Moris, Alberto Ocana
Antibody–drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization
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Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers J. Hematol. Oncol. (IF 29.5) Pub Date : 2023-12-12 Anja Seckinger, Sara Majocchi, Valéry Moine, Lise Nouveau, Hoang Ngoc, Bruno Daubeuf, Ulla Ravn, Nicolas Pleche, Sebastien Calloud, Lucile Broyer, Laura Cons, Adeline Lesnier, Laurence Chatel, Anne Papaioannou, Susana Salgado-Pires, Sebastian Krämer, Ines Gockel, Florian Lordick, Krzysztof Masternak, Yves Poitevin, Giovanni Magistrelli, Pauline Malinge, Limin Shang, Sonja Kallendrusch, Klaus Strein
T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA). We present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light