Journal of Hematology & Oncology最新文献

{"title":"Personalized nanovaccines for treating solid cancer metastases.","authors":"Tang Feng, Jia Hu, Jirui Wen, Zhiyong Qian, Guowei Che, Qinghua Zhou, Lingling Zhu","doi":"10.1186/s13045-024-01628-4","DOIUrl":"10.1186/s13045-024-01628-4","url":null,"abstract":"<p><p>Cancer vaccines have garnered attention as a potential treatment for cancer metastases. Nevertheless, the clinical response rate to vaccines remains < 30%. Nanoparticles stabilize vaccines and improve antigen recognition and presentation, resulting in high tumor penetration or accumulation, effective co-distribution of drugs to the secondary lymphatic system, and adaptable antigen or adjuvant administration. Such vaccine-like nanomedicines have the ability to eradicate the primary tumors as well as to prevent or eliminate metastases. This review examines state-of-the-art nanocarriers developed to deliver tumor vaccines to metastases, including synthetic, semi-biogenic, and biogenic nanosystems. Moreover, it highlights the physical and pharmacological properties that enhance their anti-metastasis efficiency. This review also addresses the combination of nanovaccines with cancer immunotherapy to target various steps in the metastatic cascade, drawing insights from preclinical and clinical studies. The review concludes with a critical analysis of the challenges and frameworks linked to the clinical translation of cancer nanovaccines.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"115"},"PeriodicalIF":29.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750943","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":"Evasion of immunosurveillance by the upregulation of Siglec15 in bladder cancer.","authors":"Dingshan Deng, Jiatong Xiao, Jinhui Liu, Huihuang Li, Minghui Hu, Bohan Zhou, Haisu Liang, Benyi Fan, Jinbo Chen, Xiaogen Kuang, Zhenyu Nie, Jiao Hu, Xiongbing Zu","doi":"10.1186/s13045-024-01638-2","DOIUrl":"10.1186/s13045-024-01638-2","url":null,"abstract":"<p><p>Immunotherapy resistance in bladder cancer (BLCA) is associated with elevated levels of sialic acid-binding immunoglobulin-like lectin (Siglec15). This protein plays a crucial role in fostering a noninflammatory tumor microenvironment (TME), which is conducive to cancer progression. Our study confirmed that the overexpression of Siglec15 led to a reduction in CD8⁺ T cell infiltration. This effect was mediated by the downregulation of pro-inflammatory cytokines and chemokines, which in turn exacerbated BLCA malignancy. Furthermore, Siglec15 inhibited the cytotoxicity of effector T cell, contributing to immune evasion. An in vivo study demonstrated that Siglec15 overexpression induced a non-inflammatory TME and promoted resistance to immunotherapy. These findings highlight Siglec15 as a potential therapeutic target for BLCA. By modulating inflammation in the TME and CD8⁺ T cell function, targeting Siglec15 may offer a novel strategy for overcoming immunotherapy resistance and improving patient outcomes.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"117"},"PeriodicalIF":29.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750862","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":"A clinical study of autologous chimeric antigen receptor macrophage targeting mesothelin shows safety in ovarian cancer therapy.","authors":"Xiumin Li, Xudong Wang, Hao Wang, Donghua Zuo, Jianpo Xu, Yixuan Feng, Dixuan Xue, Li Zhang, Lin Lin, Jin Zhang","doi":"10.1186/s13045-024-01635-5","DOIUrl":"10.1186/s13045-024-01635-5","url":null,"abstract":"<p><p>CAR-macrophage has promising prospect in treating solid tumors, due to its high infiltration into tumors, and its dual roles in phagocytosis and immune modulation. Here we show the clinical results of CAR-macrophage treatment of two ovarian cancer patients. The CAR-macrophages were produced by introducing a mesothelin targeting CAR to patients' primary peripheral blood mononuclear cell-derived macrophages, and the products were infused to patients intravenously. Our data show good safety of the infusion product, and the efficacy can be further improved. Intraperitoneal infusion of CAR-macrophages has proven effective in treating intraperitoneal tumors in a preclinical model, paving the way for demonstrating proof-of-concept clinical efficacy of CAR-macrophages in the treatment of intraperitoneal tumors.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"116"},"PeriodicalIF":29.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750855","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":"Dynamically monitoring minimal residual disease using circulating tumour cells to predict the recurrence of early-stage lung adenocarcinoma","authors":"Qi Zhang, Xiaoli Zhang, Zhuoheng Lv, Huandong Huo, Ligong Yuan, Duo Wan, Peipei Xie, Shujun Cheng, Kaitai Zhang, Wen Zhang, Yousheng Mao","doi":"10.1186/s13045-024-01637-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01637-3","url":null,"abstract":"Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related deaths worldwide, with a 5-year survival rate of approximately 19%. With the advent of screening and diagnostic techniques such as low-dose spiral CT and liquid biopsy, the detection rate of early stage LUAD is increasing. Even in stage I LUAD, the cumulative 5-year recurrence rate after radical surgical resection is 17.9%. This may be related to the presence of microscopic residual disease (MRD), a potential source of recurrence and metastasis. Circulating tumour cells (CTCs) are key biomarkers in liquid biopsies, but the ability of dynamic CTC detection to monitor MRD and warn of recurrence in patients with early LUAD has not been validated. Here, we conducted a prospective study using the telomerase reverse transcriptase-based CTC detection method (TBCD) to evaluate perioperative and follow-up CTC levels for dynamic monitoring to evaluate its clinical efficacy in predicting postoperative recurrence in early-stage LUAD. By longitudinal dynamic monitoring of CTC, we accurately predicted recurrence within 2 years after surgery, with an AUC of 0.9786, demonstrating the clinical values of CTC in predicting recurrence. The median lead time from positive detection of CTC to radiological recurrence was 183 days, with the earliest CT recurrence predicted 354 days in advance. Taken together, our study demonstrates that longitudinal monitoring of CTC is effective in early warning of LUAD recurrence and provides valuable information on early detection and intervention strategies for the management of LUAD.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead.","authors":"Kalyan V G Nadiminti, Kieran D Sahasrabudhe, Hongtao Liu","doi":"10.1186/s13045-024-01632-8","DOIUrl":"10.1186/s13045-024-01632-8","url":null,"abstract":"<p><p>The AML treatment landscape has significantly changed in recent years with the approval of targeted therapies in the front-line and relapsed/refractory settings, including inhibitors of FLT3 and IDH1/2 mutations. More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Even with all this exciting progress, more targeted therapies for AML treatment are needed. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"113"},"PeriodicalIF":29.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668288","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":"Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis","authors":"Samuel Urrutia, Hagop M. Kantarjian, Farhad Ravandi-Kashani, Carlos Bueso-Ramos, Rashmi Kanagal-Shamanna, Elias Jabbour, Guillermo Montalban-Bravo, Nicholas J. Short, Naval Daver, Gautam Borthakur, Courtney D. Dinardo, Tapan M. Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki","doi":"10.1186/s13045-024-01630-w","DOIUrl":"https://doi.org/10.1186/s13045-024-01630-w","url":null,"abstract":"The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0–1 and 148 (30.1%) had MF grade 2–3. Patients with MF 2–3 had a higher proportion of complex cytogenetics (39.2% vs. 24.7%, p = 0.002) JAK2 mutations (25.7% vs. 18%, p = 0.07) and lower proportion of IDH2 (16.9% vs. 25.9%, p = 0.03) and CEBPA (15.5% vs. 27.6%, p = 0.006) mutations. 64% were treated with low-intensity chemotherapy (LIT) and 36.1% with intensive chemotherapy (IT). The complete remission (CR)/CR with incomplete count recovery (CRi) rates were 63.5% with IC versus 37.9% with LIT (p = 0.007). In patients aged 60 or older 4-week mortality was 12.5% with IC vs. 9.3% with LIT (p = 0.8). The median overall survival (OS) was 14.2 with MF 0–1 versus 7.5 months with MF 2–3 (p < 0.005). In patients aged 60 or older with MF 2–3 median OS was 6.5 months with IT versus 7.0 months with LIT (p = 0.19). In a multivariate analysis, grade 2–3 MF (HR 2.0, 95%CI 1.59–2.51) was the strongest prognostic factor for survival. In summary, grade 2–3 MF in AML is associated with worse outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quizartinib: a potent and selective FLT3 inhibitor for the treatment of patients with FLT3-ITD–positive AML","authors":"Jorge Cortes","doi":"10.1186/s13045-024-01617-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01617-7","url":null,"abstract":"Mutations in FMS-related receptor tyrosine kinase 3 (FLT3) are among the most common alterations in acute myeloid leukemia (AML), present in ≈30% of newly diagnosed AML cases. Internal tandem duplications (ITD) in FLT3 (FLT3-ITD) occur in ≈25% of newly diagnosed AML cases and are associated with unfavorable outcomes. Quizartinib (formerly AC220) is a novel, second-generation, highly potent, and selective type II FLT3 inhibitor. Quizartinib is approved in Japan as monotherapy for the treatment of adult patients with FLT3-ITD–positive relapsed/refractory (R/R) AML. Quizartinib is also approved in the United States, Japan, Europe, and United Kingdom in combination with chemotherapy during induction and consolidation, and as maintenance monotherapy (but, in the United States, not after allogeneic hematopoietic cell transplantation [allo-HCT]), for the treatment of adult patients with newly diagnosed FLT3-ITD–positive AML. In this review, we summarize preclinical studies that established quizartinib as a potent and selective type II FLT3 inhibitor as well as early and pivotal phase 3 clinical studies (QuANTUM-R and QuANTUM-First) that led to the approvals of quizartinib. We also summarize mechanisms of resistance to quizartinib along with its safety profile. Furthermore, we review the ongoing post hoc analyses of the QuANTUM-First data elucidating the impact of allo-HCT, the presence of measurable residual disease, and number and length of ITD on the clinical outcomes of quizartinib. We also describe the impact of quizartinib on patient-reported outcomes. Finally, we highlight some of the ongoing studies that test quizartinib in patients with FLT3-ITD–positive AML, patients with FLT3-ITD–negative AML, in both the first-line and R/R settings, in patients fit or unfit for intensive chemotherapy, including studies for quizartinib-based combination with other compounds such as decitabine and venetoclax. Future research should aim to further optimize the clinical value of quizartinib and explore its use in additional clinical settings, which could be achieved by testing quizartinib with other drugs, better characterization of the mechanisms of resistance, identification of the role of quizartinib as a maintenance therapy after allo-HCT, and investigating quizartinib in patients with FLT3-ITD–negative AML.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"51 3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo gene editing and in situ generation of chimeric antigen receptor cells for next-generation cancer immunotherapy","authors":"Weiyue Zhang, Xin Huang","doi":"10.1186/s13045-024-01633-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01633-7","url":null,"abstract":"Chimeric antigen receptor (CAR) cell therapy has achieved groundbreaking success in treating hematological malignancies. However, its application to solid tumors remains challenging due to complex manufacturing processes, limited in vivo persistence, and transient therapeutic effects. In vivo CAR-immune cells induced by gene delivery systems loaded with CAR genes and gene-editing tools have shown efficiency for anti-tumor immunotherapy. In situ programming of autologous immune cells avoids the safety concerns of allogeneic immune cells, and the manufacture of gene delivery systems could be standardized. Therefore, the in vivo editing and in situ generation of CAR-immune cells might potentially overcome the abovementioned limitations of current CAR cell therapy. This review mainly focuses on CAR structures, gene-editing tools, and gene delivery techniques applied in anti-tumor immunotherapy to help design and develop in situ CAR-immune cell therapy. The recent applications of in vivo CAR-immune cell therapy in both hematologic malignancies and solid tumors are investigated. To sum up, the in vivo editing and in situ generation of CAR therapy holds promise for offering a practical, cost-effective, efficient, safe, and widely applicable approach to the next-generation anti-tumor immunotherapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"63 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iparomlimab (QL1604) in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic solid tumors: a pivotal, single-arm, multicenter, phase II trial","authors":"Feng Bi, Jian Dong, Chuan Jin, Zuoxing Niu, Wenhui Yang, Yifu He, Dajun Yu, Meili Sun, Teng Wang, Xianli Yin, Ruixing Zhang, Kehe Chen, Keming Wang, Zhiwu Wang, Wei Li, Zhongtao Zhang, Hangyu Zhang, Qunyi Guo, Xin Wang, Lei Han, Xizhi Zhang, Wei Shen, Liangming Zhang, Jieer Ying, Miao Wu, Weiguo Hu, Zeng Li, Xiaofen Li, Wenlei Feng, Baihui Zhang, Lingyan Li, Xiaoyan Kang, Weijian Guo","doi":"10.1186/s13045-024-01627-5","DOIUrl":"https://doi.org/10.1186/s13045-024-01627-5","url":null,"abstract":"Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight < 40 kg, IV, Q3W) until disease progression, intolerable toxicities, withdrawal of consent, death, or up to 2 years. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC). Totally, 120 patients were enrolled, of whom 60 patients failed from prior standard therapy, were enrolled in the full analysis set (FAS). As of Jan 20, 2024, the confirmed ORR per IRRC in FAS were 50.0% (30/60; 95% CI 36.8–63.2%) patients, including 4 (6.7%) complete response (CR) and 26 (43.3%) partial response (PR). In colorectal cancer (CRC) patients in FAS, the ORR reached 57.9% (22/38; 95% CI 40.8–73.7%) per IRRC, with 3 (7.9%) CR and 19 (50.0%) PR. Furtherly, the ORRs in liver metastatic or non-liver metastatic CRC patients were 52.9% (9/17, 95% CI 27.8–77.0%) vs 61.9% (13/21, 95% CI 38.4%–81.9%). The incidence of TRAE was 90.8% (any grade) and 20.8% (grade ≥ 3). Immune-related adverse events occurred in 33.3% (any grade) and 5.0% (grade ≥ 3) of patients. No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile. Trial registration ClinicalTrials.gov Identifier: NCT04326829.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"4 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms","authors":"Xiaojuan Yang, Hong Wu","doi":"10.1186/s13045-024-01631-9","DOIUrl":"https://doi.org/10.1186/s13045-024-01631-9","url":null,"abstract":"Variants in the RAS family (HRAS, NRAS and KRAS) are among the most common mutations found in cancer. About 19% patients with cancer harbor RAS mutations, which are typically associated with poor clinical outcomes. Over the past four decades, KRAS has long been considered an undruggable target due to the absence of suitable small-molecule binding sites within its mutant isoforms. However, recent advancements in drug design have made RAS-targeting therapies viable, particularly with the approval of direct KRASG12C inhibitors, such as sotorasib and adagrasib, for treating non-small cell lung cancer (NSCLC) with KRASG12C mutations. Other KRAS-mutant inhibitors targeting KRASG12D are currently being developed for use in the clinic, particularly for treating highly refractory malignancies like pancreatic cancer. Herein, we provide an overview of RAS signaling, further detailing the roles of the RAS signaling pathway in carcinogenesis. This includes a summary of RAS mutations in human cancers and an emphasis on therapeutic approaches, as well as de novo, acquired, and adaptive resistance in various malignancies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"2 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596945","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}