{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:26:08Z","timestamp":1792031168486,"version":"4.4.0"},"reference-count":214,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-041"],"award-info":[{"award-number":["2021-I2M-1-041"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["Z211100002921016"],"award-info":[{"award-number":["Z211100002921016"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2022-PUMCH-A-021"],"award-info":[{"award-number":["2022-PUMCH-A-021"]}]},{"name":"Research and Translation Application of Beijing Clinical Diagnostic Technologies Funds from Beijing Municipal Commission of Science and Technology","award":["2021-I2M-1-041"],"award-info":[{"award-number":["2021-I2M-1-041"]}]},{"name":"Research and Translation Application of Beijing Clinical Diagnostic Technologies Funds from Beijing Municipal Commission of Science and Technology","award":["Z211100002921016"],"award-info":[{"award-number":["Z211100002921016"]}]},{"name":"Research and Translation Application of Beijing Clinical Diagnostic Technologies Funds from Beijing Municipal Commission of Science and Technology","award":["2022-PUMCH-A-021"],"award-info":[{"award-number":["2022-PUMCH-A-021"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2021-I2M-1-041"],"award-info":[{"award-number":["2021-I2M-1-041"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["Z211100002921016"],"award-info":[{"award-number":["Z211100002921016"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-021"],"award-info":[{"award-number":["2022-PUMCH-A-021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target multiple antigens and overcome individual limitations. Despite these advancements, some shortcomings prevent the widespread use of CAR-T therapy, including life-threatening toxicities, T-cell exhaustion, and inadequate infiltration for solid tumors. Researchers have made considerable efforts to address these issues by developing new strategies for improving CAR-T cell function and reducing toxicities. This review provides an overview of the path of CAR-T cell development and highlights some of the prominent advances in its structure and manufacturing process, which include the strategies to improve antigen recognition, enhance T-cell activation and persistence, and overcome immune escape. Finally, the review briefly covers other immune cells for cancer therapy and ends with the discussion on the broad prospects of CAR-T in the treatment of various diseases, not just hematological tumors, and the challenges that need to be addressed for the widespread clinical application of CAR-T cell therapies.<\/jats:p>","DOI":"10.3390\/cancers15133476","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:38:32Z","timestamp":1688434712000},"page":"3476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhibo","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-3571","authenticated-orcid":false,"given":"Siyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daobin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. 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