{"title":"Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy","authors":"Weihuan Shao, Yiran Yao, Ludi Yang, Xiaoran Li, Tongxin Ge, Yue Zheng, Qiuyi Zhu, Shengfang Ge, Xiang Gu, Renbing Jia, Xin Song, Ai Zhuang","doi":"10.1186/s40164-024-00504-8","DOIUrl":null,"url":null,"abstract":"Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"46 1","pages":""},"PeriodicalIF":9.4000,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40164-024-00504-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.
T 细胞的适应性免疫疗法在癌症治疗中显示出疗效。过去几十年来,转基因 T 细胞,特别是嵌合抗原受体 T 细胞在治疗血液恶性肿瘤方面取得了显著进展。此外,对治疗实体瘤的多种抗原的广泛探索,也使临床对表达工程化 T 细胞受体(TCR)的 T 细胞的潜力产生了兴趣。TCR-T 细胞具有识别细胞内抗原家族的能力,并在与目标表位的亲和力和信号转导方面保持 TCR 的固有特性。最近的研究对TCR-T细胞的能力和多种难治性实体瘤的治疗靶点提出了重要的见解,但也暴露出了持久疗效方面的一些挑战。在这篇综述中,我们介绍了现有肿瘤抗原的筛选和鉴定,以及用于 TCR-T 细胞疗法的 TCR 的获取和优化。此外,我们还总结了 TCR-T 细胞从实验室到临床应用的完整流程。最后,我们展望了利用联合疗法或 TCR-T 衍生产品提高癌症疗效的未来前景。总之,这篇综述描述了我们目前对实体瘤 TCR-T 细胞疗法的理解,并为扩大其临床应用和提高疗效提供了新的视角。
期刊介绍:
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.