Experimental Hematology & Oncology最新文献

{"title":"Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma.","authors":"Jingjing Pu, Ting Liu, Amit Sharma, Liping Jiang, Feng Wei, Xiubao Ren, Ingo G H Schmidt-Wolf, Jian Hou","doi":"10.1186/s40164-024-00576-6","DOIUrl":"10.1186/s40164-024-00576-6","url":null,"abstract":"<p><p>The basic idea of modulating the immune system to better recognize and fight tumor cells has led to the successful introduction of adoptive cellular immunotherapy (ACT). ACT-based treatment regimens, in which the patient's own immune cells are isolated and subsequently expanded (ex vivo) and reinfused, have also contributed significantly to the development of a personalized treatment strategy. Complementing this, the unprecedented advances in ACTs as chimeric antigen receptor (CAR)-T cell therapies and their derivatives such as CAR-NK, CAR-macrophages, CAR-γδT and CAR-NKT have further maximized the therapeutic outcomes. Herein, we provide a comprehensive overview of the development of ACTs in multiple myeloma (MM) and outline how they have evolved from an experimental form to a mainstay of standard clinical settings. Besides, we provide insights into cytokine-induced killer cell (CIK) therapy, an alternative form of ACT that (as CIK or CAR-CIK) has enormous potential in the clinical spectrum of MM. We also summarize the results of the major preclinical and clinical studies of adoptive cell therapy in MM and address the current challenges (such as cytokine release syndrome (CRS) and neurotoxicity) that limit its complete success in the cancer landscape.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"105"},"PeriodicalIF":9.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD5 chimeric antigen receptor-engineered natural killer cells against T-cell malignancies.","authors":"Yingling Zu, Quan Ren, Jishuai Zhang, Hongchang Su, Qiumei Lu, Yongping Song, Jian Zhou","doi":"10.1186/s40164-024-00577-5","DOIUrl":"10.1186/s40164-024-00577-5","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor engineered T cells (CAR-T) have demonstrated promising clinical efficacy in B-cell malignancies, and the approach has been extended to T-cell malignancies. However, the use of allogeneic T cells in CAR therapy poses a challenge due to the risk of graft-versus-host disease. Recently, natural killer (NK) cells have exhibited \"off‑the‑shelf\" availability. The nanobody-based CAR structures have attracted much attention for their therapeutic potential owing to the advantages of nanobody, including small size, optimal stability, high affinity and manufacturing feasibility. CD5, a common surface marker of malignant T cells, has three scavenger receptor cysteine-rich domains (D1-D3) in the extracellular region. The present study aims to construct \"off‑the‑shelf\" CAR-NK cells targeting the membrane-proximal domain of CD5 derived from nanobody against T-cell malignancies.</p><p><strong>Methods: </strong>Anti-CD5-D3 nanobody was screened by phage display technology, followed by constructing fourth-generation CAR plasmids ectopically producing IL-15 to generate CD5 CAR-NK cells derived from peripheral blood. And the second-generation CD5 CAR-T cells based on nanobody were generated, referred to as 5D.b CAR-T and 12 C.b CAR-T. Furthermore, CAR-NK cells without IL-15 (IL-15^△ CAR-NK) were generated to assess the impact on cytotoxicity of CAR-NK cells. Cytotoxic activity against CD5⁺ hematologic malignant cell lines and normal T cells was exerted in vitro and NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mouse model transplanted with Jurkat-Luc cells was used to evaluate the antitumor efficacy of CD5 CAR-NK cells in vivo.</p><p><strong>Results: </strong>Two nanobodies (5D and 12 C) competed for binding to the epitope of CD5-D3. 12 C CAR-NK cells were superior to 5D CAR-NK cells in antitumor potential and 12 C.b CAR-T cells exhibited superior cytotoxic activity than 5D CAR-T cells ex vivo. So, 12 C was regarded as the optimal nanobody. 12 C CAR-NK cells and IL-15^△ CAR-NK cells exhibited robust cytotoxicity against CD5⁺ malignant cell lines and controlled disease progression in xenograft mouse model. 12 C CAR-NK cells demonstrated greater antitumor activity compared to that of IL-15^△ CAR-NK cells in vitro and in vivo.</p><p><strong>Conclusions: </strong>Taken together, the fourth-generation nanobody-derived anti-CD5 CAR-NK cells may be a promising therapeutic against T-cell malignancies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"104"},"PeriodicalIF":9.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing CD8⁺ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators.","authors":"Zihao Zhou, Jiarong Zheng, Ye Lu, Zizhao Mai, Yunfan Lin, Pei Lin, Yucheng Zheng, Xu Chen, Rongwei Xu, Xinyuan Zhao, Li Cui","doi":"10.1186/s40164-024-00575-7","DOIUrl":"https://doi.org/10.1186/s40164-024-00575-7","url":null,"abstract":"<p><p>CD8⁺ T cells are integral to the effective management of cancer and infectious diseases due to their cytotoxic functions. The efficacy of these cells is profoundly influenced by their metabolic state, which regulates their activation, differentiation, and longevity. Accordingly, the modulation of metabolic pathways within CD8⁺ T cells is crucial for enhancing the effectiveness of T cell-based immunotherapy. Precise metabolic control is paramount in optimizing therapeutic outcomes and minimizing potential toxicities associated with treatment. Importantly, the potential of exogenous metabolites to augment CD8⁺ T cell responses is critically evaluated, especially through in vivo evidence that underscores their therapeutic promise. This review also addresses current challenges, including the need for precise control of metabolic modulation to avoid adverse effects, the development of targeted delivery systems to ensure efficient metabolite delivery to CD8⁺ T cells, and the inherent variability of metabolic states among patients that may influence treatment outcomes. Addressing these hurdles will be crucial for the successful integration of metabolic interventions into established immunotherapeutic regimens.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"103"},"PeriodicalIF":9.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 technology for advancements in cancer immunotherapy: from uncovering regulatory mechanisms to therapeutic applications.","authors":"Xiaohang Feng, Zhengxing Li, Yuping Liu, Di Chen, Zhuolong Zhou","doi":"10.1186/s40164-024-00570-y","DOIUrl":"https://doi.org/10.1186/s40164-024-00570-y","url":null,"abstract":"<p><p>In recent years, immunotherapy has developed rapidly as a new field of tumour therapy. However, the efficacy of tumour immunotherapy is not satisfactory due to the immune evasion mechanism of tumour cells, induction of immunosuppressive tumour microenvironment (TME), and reduction of antigen delivery, etc. CRISPR/Cas9 gene editing technology can accurately modify immune and tumour cells in tumours, and improve the efficacy of immunotherapy by targeting immune checkpoint molecules and immune regulatory genes, which has led to the great development and application. In current clinical trials, there are still many obstacles to the application of CRISPR/Cas9 in tumour immunotherapy, such as ensuring the accuracy and safety of gene editing, overcoming overreactive immune responses, and solving the challenges of in vivo drug delivery. Here we provide a systematic review on the application of CRISPR/Cas9 in tumour therapy to address the above existing problems. We focus on CRISPR/Cas9 screening and identification of immunomodulatory genes, targeting of immune checkpoint molecules, manipulation of immunomodulators, enhancement of tumour-specific antigen presentation and modulation of immune cell function. Second, we also highlight preclinical studies of CRISPR/Cas9 in animal models and various delivery systems, and evaluate the efficacy and safety of CRISPR/Cas9 technology in tumour immunotherapy. Finally, potential synergistic approaches for combining CRISPR/Cas9 knockdown with other immunotherapies are presented. This study underscores the transformative potential of CRISPR/Cas9 to reshape the landscape of tumour immunotherapy and provide insights into novel therapeutic strategies for cancer patients.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"102"},"PeriodicalIF":9.4,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural killer cell-based cancer immunotherapy: from basics to clinical trials.","authors":"Yinghong Shi, Donglin Hao, Hui Qian, Zhimin Tao","doi":"10.1186/s40164-024-00561-z","DOIUrl":"https://doi.org/10.1186/s40164-024-00561-z","url":null,"abstract":"<p><p>Cellular immunotherapy exploits the capacity of the human immune system in self-protection and surveillance to achieve the anti-tumor effects. Natural killer (NK) cells are lymphocytes of innate immune system and they display a unique inherent ability to identify and eliminate tumor cells. In this review, we first introduce the basic characteristics of NK cells in the physiological and pathological milieus, followed by a discussion of their effector function and immunosuppression in the tumor microenvironment. Clinical strategies and reports regarding NK cellular therapy are analyzed in the context of tumor treatment, especially against solid tumors. Given the widely studied T-cell therapy in the recent years, particularly the chimeric antigen receptor (CAR) T-cell therapy, we compare the technical features of NK- and T-cell based tumor therapies at the clinical front. Finally, the technical challenges and potential solutions for both T and NK cell-based immunotherapies in treating tumor malignancies are delineated. By overviewing its clinical applications, we envision the NK-cell based immunotherapy as an up-and-comer in cancer therapeutics.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"101"},"PeriodicalIF":9.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD19/CD22 CAR-T-cell cocktail therapy following autologous transplantation is an optimizing strategy for treating relapsed/refractory central nervous system lymphoma.","authors":"Xiaoxi Zhou, Qiuxia Yu, Zigang Dai, Jue Wang, Chunrui Li, Liang Huang, Yicheng Zhang, Yang Cao","doi":"10.1186/s40164-024-00538-y","DOIUrl":"https://doi.org/10.1186/s40164-024-00538-y","url":null,"abstract":"<p><p>Relapsed/refractory (R/R) primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. We retrospectively compared the safety and efficacy of CD19/22 CAR-T-cell therapy following ASCT (ASCT + CAR-T group), CD19/22 CAR-T-cell cocktail therapy (CAR-T group) and chemoimmunotherapy (CIT group) in treating R/R CNSL patients. Analysis of the differences in clinical characteristics among the three groups revealed that the median age in the CIT group was older than that in the ASCT + CAR-T group and CAR-T group, and the median number of prior lines of therapy in the CIT group was less than that in the other groups. Patients in the two CAR-T-therapy groups exhibited comparable incidences and severities of CRS and ICANS. Grade 4-5 CRS and ICANS were not observed in either CAR-T-cell therapy group. The incidence of Grade 3/4 hematological toxicity in the ASCT + CAR-T and CAR-T groups was greater than that in the CIT group. The ORR was 82.75% in the ASCT + CAR-T group, 60.00% in the CAR-T group and 58.83% in the CIT group. As of December 31, 2022, the median follow-up after therapy was 16.73 months (range, 0.67-42.00 months). The median durations of PFS and OS were not reached in the ASCT + CAR-T group. The median PFS in the CAR-T group was 4.72 months, and OS was not reached. In the CIT group, the median PFS and OS were 6.63 months and 16.77 months, respectively. The 2-year PFS rate of patients in the ASCT + CAR-T group (65.52%) was significantly greater than that of patients in the CAR-T group (30.00%, P = 0.0321) and CIT group (23.53%, P = 0.0043). Our results support the development of CAR-T-cell therapy for R/R CNSL. With the durability of remission and low toxicity, ASCT combined with CAR-T-cell therapy appears to be a more effective and safer treatment option for primary and secondary R/R CNS lymphoma.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"100"},"PeriodicalIF":9.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.","authors":"Niels Vandewalle, Nathan De Beule, Ann De Becker, Elke De Bruyne, Eline Menu, Karin Vanderkerken, Karine Breckpot, Nick Devoogdt, Kim De Veirman","doi":"10.1186/s40164-024-00566-8","DOIUrl":"10.1186/s40164-024-00566-8","url":null,"abstract":"<p><p>Until recently, treatment options for patients diagnosed with Acute Myeloid Leukemia (AML) were limited and predominantly relied on various combinations, dosages, or schedules of traditional chemotherapeutic agents. Patients with advanced age, relapsed/refractory disease or comorbidities were often left without effective treatment options. Novel advances in the understanding of leukemogenesis at the molecular and genetic levels, alongside recent progress in drug development, have resulted in the emergence of novel therapeutic agents and strategies for AML patients. Among these innovations, the receptor tyrosine kinase AXL has been established as a promising therapeutic target for AML. AXL is a key regulator of several cellular functions, including epithelial-to-mesenchymal transition in tumor cells, immune regulation, apoptosis, angiogenesis and the development of chemoresistance. Clinical studies of AXL inhibitors, as single agents and in combination therapy, have demonstrated promising efficacy in treating AML. Additionally, novel AXL-targeted therapies, such as AXL-specific antibodies or antibody fragments, present potential solutions to overcome the limitations associated with traditional small-molecule AXL inhibitors or multikinase inhibitors. This review provides a comprehensive overview of the structure and biological functions of AXL under normal physiological conditions, including its role in immune regulation. We also summarize AXL's involvement in cancer, with a specific emphasis on its role in the pathogenesis of AML, its contribution to immune evasion and drug resistance. Moreover, we discuss the AXL inhibitors currently undergoing (pre)clinical evaluation for the treatment of AML.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"99"},"PeriodicalIF":9.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined inhibition of MET and VEGF enhances therapeutic efficacy of EGFR TKIs in EGFR-mutant non-small cell lung cancer with concomitant aberrant MET activation.","authors":"Shanshan Huang, Yaling Long, Yuan Gao, Wanling Lin, Lei Wang, Jizong Jiang, Xun Yuan, Yuan Chen, Peng Zhang, Qian Chu","doi":"10.1186/s40164-024-00565-9","DOIUrl":"10.1186/s40164-024-00565-9","url":null,"abstract":"<p><strong>Background: </strong>Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined.</p><p><strong>Methods: </strong>The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo.</p><p><strong>Results: </strong>We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case.</p><p><strong>Conclusions: </strong>Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"97"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical investigations and a first-in-human phase 1a trial of JS007, a novel anti-CTLA-4 antibody, in patients with advanced solid tumors.","authors":"Chenfei Zhou, Jinling Jiang, Xiaojun Xiang, Hongli Liu, Guowu Wu, Ruichao Zeng, Tong Lu, Mengqi Zhang, Yuteng Shen, Min Hong, Jun Zhang","doi":"10.1186/s40164-024-00567-7","DOIUrl":"10.1186/s40164-024-00567-7","url":null,"abstract":"<p><strong>Background: </strong>Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) shows substantial antitumor efficacy. Here, we report the preclinical data and outcomes of a first-in-human phase 1a trial of JS007, a novel anti-CTLA-4 antibody, in advanced solid tumors.</p><p><strong>Methods: </strong>In preclinical studies, both in vitro characteristics and in vivo characteristics of JS007 were investigated. The clinical trial included a dose escalation phase and a dose expansion phase. Eligible patients with previously treated advanced solid tumors were enrolled. In the dose escalation phase, JS007 was administered intravenously every 3 weeks at doses of 0.03, 0.3, 1, 3, and 10 mg/kg. Then, 3 and 10 mg/kg were chosen for the dose expansion phase. The primary endpoints included the maximum tolerated dose (MTD) of JS007 based on dose-limiting toxicities (DLTs) and safety.</p><p><strong>Results: </strong>JS007 could effectively bind to CTLA-4 and induce an immune response in vitro. Potent in vivo antitumor activity of JS007 was observed. Increased T cell infiltration and T regulatory (Treg) cell depletion in tumor microenvironment of cancer cell xenografts were detected after treated with JS007. Pharmacological analysis in experimental animals showed a dose-proportional increase in exposure. In the clinical trial, a total of 28 patients were treated with JS007 across 5 dose levels. No DLTs occurred. The MTD did not reach at the highest dose tested (10 mg/kg). Twenty-three (82.1%) patients experienced at least one treatment-related adverse event (TRAE). The incidence of Grade ≥ 3 TRAEs was 28.6% (8/28) with alanine aminotransferase increase (7.1%, 2/28) being the most frequently reported TRAE. No severe immune-related adverse event (irAE) occurred. Pharmacological profiles of JS007 in patients were similar to those in animal models. Serum concentration of JS007 showed a dose-dependent escalation, and the half-life of JS007 was 9.4 ~ 12.2 days. Treatment-induced anti-drug antibody was detected in 2 patients. The disease control rate was 50% (14/28), and the median overall survival was 14.7 months.</p><p><strong>Conclusions: </strong>JS007 preliminarily demonstrates good tolerance and encouraging antitumor activity in patients with previously treated advanced solid tumors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT05049265 (Sep 20, 2021).</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"98"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.","authors":"Xianjun Li, Tianjun Chen, Xuehan Li, Hanyu Zhang, Yingjing Li, Shuyuan Zhang, Shengnan Luo, Tongsen Zheng","doi":"10.1186/s40164-024-00564-w","DOIUrl":"10.1186/s40164-024-00564-w","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies. However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy. In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy. Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"96"},"PeriodicalIF":9.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}