Ning Jiang, Zhaoyi Yang, Huilei Miao, Shujun Xing, Shuhang Wang, Ning Li
{"title":"通用嵌合抗原受体T细胞治疗的最新进展","authors":"Ning Jiang, Zhaoyi Yang, Huilei Miao, Shujun Xing, Shuhang Wang, Ning Li","doi":"10.1186/s13045-025-01737-8","DOIUrl":null,"url":null,"abstract":"While chimeric antigen receptor (CAR) T cell therapy is highly effective for hematological malignancies, its widespread use is limited by complex, patient-specific manufacturing. Universal CAR-T (UCAR-T) cells, derived from allogeneic donors, offer a potential \"off-the-shelf\" solution. However, their clinical translation hinges on overcoming two key immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR), which compromise safety and therapeutic persistence. This review summarizes recent advances in UCAR-T cell engineering and clinical strategies designed to improve both safety and efficacy. We discuss gene-editing technologies—such as CRISPR/Cas9 and base editors—used to prevent GvHD by ablating the T cell receptor (TCR) and to evade HvGR by disrupting human leukocyte antigen (HLA) expression. We also explore the development of UCAR-T products from alternative cell sources with low intrinsic alloreactivity, such as γδ T cells. Furthermore, we detail multifaceted approaches to augment UCAR-T cell function and persistence, from the perspectives of enhancing intrinsic functions, reshaping the tumor microenvironment (TME) and overcoming tumor heterogeneity. Finally, we analyze recent clinical trial outcomes, which show promising efficacy in hematological malignancies but highlight ongoing challenges in solid tumors. The continued integration of sophisticated cellular engineering with innovative clinical strategies—such as enhanced lymphodepletion, combination therapies, and alternative administration routes—will be essential to realize the full potential of UCAR-T as a widely accessible and potent cell therapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"29 1","pages":""},"PeriodicalIF":40.4000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recent advances in universal chimeric antigen receptor T cell therapy\",\"authors\":\"Ning Jiang, Zhaoyi Yang, Huilei Miao, Shujun Xing, Shuhang Wang, Ning Li\",\"doi\":\"10.1186/s13045-025-01737-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"While chimeric antigen receptor (CAR) T cell therapy is highly effective for hematological malignancies, its widespread use is limited by complex, patient-specific manufacturing. Universal CAR-T (UCAR-T) cells, derived from allogeneic donors, offer a potential \\\"off-the-shelf\\\" solution. However, their clinical translation hinges on overcoming two key immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR), which compromise safety and therapeutic persistence. This review summarizes recent advances in UCAR-T cell engineering and clinical strategies designed to improve both safety and efficacy. We discuss gene-editing technologies—such as CRISPR/Cas9 and base editors—used to prevent GvHD by ablating the T cell receptor (TCR) and to evade HvGR by disrupting human leukocyte antigen (HLA) expression. We also explore the development of UCAR-T products from alternative cell sources with low intrinsic alloreactivity, such as γδ T cells. Furthermore, we detail multifaceted approaches to augment UCAR-T cell function and persistence, from the perspectives of enhancing intrinsic functions, reshaping the tumor microenvironment (TME) and overcoming tumor heterogeneity. Finally, we analyze recent clinical trial outcomes, which show promising efficacy in hematological malignancies but highlight ongoing challenges in solid tumors. The continued integration of sophisticated cellular engineering with innovative clinical strategies—such as enhanced lymphodepletion, combination therapies, and alternative administration routes—will be essential to realize the full potential of UCAR-T as a widely accessible and potent cell therapy.\",\"PeriodicalId\":16023,\"journal\":{\"name\":\"Journal of Hematology & Oncology\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":40.4000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Hematology & Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13045-025-01737-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13045-025-01737-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Recent advances in universal chimeric antigen receptor T cell therapy
While chimeric antigen receptor (CAR) T cell therapy is highly effective for hematological malignancies, its widespread use is limited by complex, patient-specific manufacturing. Universal CAR-T (UCAR-T) cells, derived from allogeneic donors, offer a potential "off-the-shelf" solution. However, their clinical translation hinges on overcoming two key immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR), which compromise safety and therapeutic persistence. This review summarizes recent advances in UCAR-T cell engineering and clinical strategies designed to improve both safety and efficacy. We discuss gene-editing technologies—such as CRISPR/Cas9 and base editors—used to prevent GvHD by ablating the T cell receptor (TCR) and to evade HvGR by disrupting human leukocyte antigen (HLA) expression. We also explore the development of UCAR-T products from alternative cell sources with low intrinsic alloreactivity, such as γδ T cells. Furthermore, we detail multifaceted approaches to augment UCAR-T cell function and persistence, from the perspectives of enhancing intrinsic functions, reshaping the tumor microenvironment (TME) and overcoming tumor heterogeneity. Finally, we analyze recent clinical trial outcomes, which show promising efficacy in hematological malignancies but highlight ongoing challenges in solid tumors. The continued integration of sophisticated cellular engineering with innovative clinical strategies—such as enhanced lymphodepletion, combination therapies, and alternative administration routes—will be essential to realize the full potential of UCAR-T as a widely accessible and potent cell therapy.
期刊介绍:
The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts.
Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.