Hematology and Oncology Discovery最新文献

T-cell engineering strategies for tumors with low antigen density, and T-cell survival in the immunosuppressive tumor microenvironment of relapsed/refractory diffuse large B-cell lymphoma 低抗原密度肿瘤的t细胞工程策略，以及复发/难治性弥漫性大b细胞淋巴瘤免疫抑制肿瘤微环境中的t细胞存活

Hematology and Oncology Discovery Pub Date : 2023-03-25 DOI: 10.15212/hod-2022-0009

Rong Luan, B. Deng

{"title":"T-cell engineering strategies for tumors with low antigen density, and T-cell survival in the immunosuppressive tumor microenvironment of relapsed/refractory diffuse large B-cell lymphoma","authors":"Rong Luan, B. Deng","doi":"10.15212/hod-2022-0009","DOIUrl":"https://doi.org/10.15212/hod-2022-0009","url":null,"abstract":"Refractory and/or relapsed (r/r) diffuse large B-cell lymphomas after treatment with two lines of systemic chemoimmunotherapy exhibit diversity in genetics, tissue biology, and pathology, as well as poor prognosis. Patient TCRαβ cells engineered with a CD19-specific chimeric antigen receptor (CAR) have shown promising clinical outcomes in r/r diffuse large B-cell lymphoma. The ZUMA-1 study, the JULIET study, and the TRANSCEND NHL 001 study of three prototype 19CAR-T cells have indicated an overall response rate of 52–82%, a complete response rate of 40–58%, and a 12-month progression-free survival of 33.2%–46.6%, with clinically manageable treatment related toxicity. At the 5-year follow-up, relapse was observed in approximately 57% of patients within 1 year. Understanding of the risk factors for non-response remains insufficient. In addition to intrinsic tumor resistance, such as aberrant apoptotic signaling, downregulation or loss of tumor-associated antigens (TAA), an immunosuppressive tumor microenvironment, and CAR-T cell exhaustion in vivo have been suggested to be important risk factors. Mechanisms underlying 19CAR-T cell exhaustion under chronic TAA exposure, and limited 19CAR-T cell trafficking and infiltration into the tumor mass have been reported. Moreover, tumor escape in the presence of low TAA density remains a challenge in 1928ζ CAR-T cell treatment. In this review, we provide an overview of modified modular CAR elements and their synergistic effects in controlling T-cell function. We then briefly discuss novel strategies against tumors with low TAA density, such as bispecific tandem or loop CAR recognition domains, the development of human leukocyte antigen-independent synthetic TCRαβ double-chain receptors integrated into the constant region of the TCRα chain, and armored CAR-T cells targeting the tumor microenvironment.","PeriodicalId":107466,"journal":{"name":"Hematology and Oncology Discovery","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127698543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges for CAR-T cell therapy in multiple myeloma: overcoming the tumor microenvironment CAR-T细胞治疗多发性骨髓瘤的挑战:克服肿瘤微环境

Hematology and Oncology Discovery Pub Date : 2023-02-15 DOI: 10.15212/hod-2022-0008

Jian Cui, G. An, L. Qiu

引用次数: 0

CD7 CAR-T therapy for an AML patient with CD7 expression CD7 CAR-T治疗一名表达CD7的AML患者

Hematology and Oncology Discovery Pub Date : 2022-12-13 DOI: 10.15212/hod-2022-0007

L. An, Ruifeng Hou, Huanhuan Guan, Zhihui Li, Tong Wu, Shuangyou Liu

{"title":"CD7 CAR-T therapy for an AML patient with CD7 expression","authors":"L. An, Ruifeng Hou, Huanhuan Guan, Zhihui Li, Tong Wu, Shuangyou Liu","doi":"10.15212/hod-2022-0007","DOIUrl":"https://doi.org/10.15212/hod-2022-0007","url":null,"abstract":"To date, no ideal CAR-T product is available for treating acute myeloid leukemia (AML). Recently, CD7 CAR-T therapy has shown promising efficiency in treating T-cell acute lymphoblastic leukemia. Because the CD7 antigen is also expressed on the myeloid blasts of some patients with AML, it might serve as a target for immunotherapy in AML. Herein, we administered CD7-specific CAR-T cells into a 20-year-old woman with AML with CD7 expression. She had a history of multiple relapses (with extramedullary disease, EMD) and treatments (radiation and allogeneic hematopoietic cell transplantation). The most recent relapse indicated a high disease burden with multifocal EMD. After a combination regimen of azacytidine, venetoclax and ruxolitinib, she showed minimal residual disease-positive remission in the bone marrow (BM), and EMD remained present. Subsequently, donor-derived CD7 CAR-T cells infused at a dose of 5.5×105/kg completely eliminated all disease in the BM and extramedullary areas. Grade I cytokine release syndrome occurred with no neurotoxicity. CD7 CAR-T cells were detectable in the peripheral blood and BM. Fifty-five days after T-cell infusion, she underwent a second allogeneic hematopoietic cell transplantation and has survived in disease-free remission for more than 7 months.","PeriodicalId":107466,"journal":{"name":"Hematology and Oncology Discovery","volume":"45 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123254410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the mechanisms of CD19 CAR T-cell failure and salvage strategies in B-cell lymphoma 探讨b细胞淋巴瘤中CD19 CAR - t细胞衰竭的机制和挽救策略

Hematology and Oncology Discovery Pub Date : 2022-10-27 DOI: 10.15212/hod-2022-0004

Fan Yang, Rui Liu, K. Hu

引用次数: 0

Whole-process management of complications during CAR-T therapy CAR-T治疗过程中并发症的全过程管理

Hematology and Oncology Discovery Pub Date : 2022-10-18 DOI: 10.15212/hod-2022-0005

Yingying Li, H. Mei

引用次数: 1

CAR-T Cell therapy in T-cell malignancies: limitations and solutions CAR-T细胞治疗t细胞恶性肿瘤:局限性和解决方案

Hematology and Oncology Discovery Pub Date : 2022-09-23 DOI: 10.15212/hod-2022-0002

Lingling Shan, Xiaoming Feng, Jing Pan

引用次数: 0

Novel bayesian adaptive early phase designs to accelerate the development of CAR T-cell therapy 新的贝叶斯自适应早期设计加速CAR - t细胞疗法的发展

Hematology and Oncology Discovery Pub Date : 2022-08-09 DOI: 10.15212/hod-2022-0003

Ying Yuan, Kai Chen

引用次数: 0

Chimeric antigen receptor engineered T-cell therapy for central nervous system lymphoma 嵌合抗原受体工程t细胞治疗中枢神经系统淋巴瘤

Hematology and Oncology Discovery Pub Date : 2022-07-19 DOI: 10.15212/hod-2022-0001

Tiantian Sun, Mi Zhou, Liang Huang

{"title":"Chimeric antigen receptor engineered T-cell therapy for central nervous system lymphoma","authors":"Tiantian Sun, Mi Zhou, Liang Huang","doi":"10.15212/hod-2022-0001","DOIUrl":"https://doi.org/10.15212/hod-2022-0001","url":null,"abstract":"Central nervous system lymphoma (CNSL) includes primary and secondary subtypes. It is associated with poor prognosis even after aggressive therapies. Primary CNSL involves mainly the brain, eyes, leptomeninges and spinal cord, without evidence of systemic non-Hodgkin’s lymphoma (NHL). Secondary CNSL refers to involvement of the CNS secondary to systemic NHL. Chimeric antigen receptor T (CAR-T) cells are genetically engineered T-cells directed against tumor target antigens. CAR-T-cells have shown encouraging results in treating B-cell malignancies. Clinical data on CAR-T-cells in CNSL treatment are limited, because of concerns regarding the immunoprivileged status of the CNS and the possibility of immune effector cell-associated neurotoxicity syndrome. Clinical trials on CAR-T therapy for CNSL are increasingly being conducted to evaluate its efficiency and safety since CAR-T-cells have been detected in the cerebrospinal fluid from a patient with PMBCL who received CAR-T-cell therapy. Current data suggest that CAR-T-cells are an emerging therapeutic modality for CNSL with clinical benefits and acceptable adverse effects. However, whether CAR-T therapy may be a promising therapeutic avenue remains controversial, because evidence from large-scale randomized clinical trials remains lacking. Herein, we provide a review of existing clinical data on CAR-T-cell therapy for CNSL, discuss the limitations of CAR-T-cells in CNSL treatment and hypothesize strategies to overcome these challenges.","PeriodicalId":107466,"journal":{"name":"Hematology and Oncology Discovery","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130589526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Base editing therapy forges ahead 碱基编辑疗法向前发展

Hematology and Oncology Discovery Pub Date : 1900-01-01 DOI: 10.15212/hod-2023-0001

Wen Jiang, Rui Yang

{"title":"Base editing therapy forges ahead","authors":"Wen Jiang, Rui Yang","doi":"10.15212/hod-2023-0001","DOIUrl":"https://doi.org/10.15212/hod-2023-0001","url":null,"abstract":"CRISPR/Cas-based gene editing is an innovative biotechnology that has revolutionized genetic engineering in recent years. The process involves induction of a double-strand break (DSB) at the desired DNA site and subsequent cellular repair. Two primary mechanisms drive DSB repair: non-homologous end joining and homologous recombination-mediated repair. Non-homologous end joining, the primary mode of DSB repair, is a simple high-efficiency process that is susceptible to errors, and unpredictable nucleotide insertion or deletion mutations. In contrast, point mutations account for more than 50% of human genetic disorders and are the most frequent type of genetic variation in nature. Base editing is a precise gene editing approach in which a single DNA base is substituted without introduction of DSBs or use of a repair template. This technique has promising therapeutic potential in gene therapy, owing to its high efficiency and controllable editing results. Since the invention of the first base editing tools, the technique has rapidly developed and undergone clinical trials. This review summarizes progress in gene therapy through base editing, including DNA and RNA base editing, with particular emphasis on recent clinical trial and preclinical research advancements, current limitations and remaining challenges, and prospects for further research and applications.","PeriodicalId":107466,"journal":{"name":"Hematology and Oncology Discovery","volume":"216 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123137968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0