{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:04:02Z","timestamp":1792404242551,"version":"4.4.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T00:00:00Z","timestamp":1674259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The year 2017 was marked by the Food and Drug Administration (FDA) approval of the first two chimeric antigen receptor-T (CAR-T) therapies. The approved indications were for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia (ALL) that is refractory or in a second or later relapse. Since then, extensive research activities have been ongoing globally on different hematologic and solid tumors to assess the safety and efficacy of CAR-T therapy for these diseases. Limitations to CAR-T therapy became apparent from, e.g., the relapse in up to 60% of patients and certain side effects such as cytokine release syndrome (CRS). This led to extensive clinical activities aimed at overcoming these obstacles, so that the use of CAR-T therapy can be expanded. Attempts to improve on efficacy and safety include changing the CAR-T administration schedule, combining it with chemotherapy, and the development of next-generation CAR-T therapies, e.g., through the use of CAR-natural killer (CAR-NK) and CAR macrophages (CAR-Ms). This review will focus on new CAR-T treatment strategies in hematologic malignancies, clinical trials aimed at improving efficacy and addressing side effects, the challenges that CAR-T therapy faces in solid tumors, and the ongoing research aimed at overcoming these challenges.<\/jats:p>","DOI":"10.3390\/cancers15030663","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:19:22Z","timestamp":1674447562000},"page":"663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":234,"title":["CAR-T: What Is Next?"],"prefix":"10.3390","volume":"15","author":[{"given":"Yi-Ju","family":"Chen","sequence":"first","affiliation":[{"name":"School of Cancer & Pharmaceutical Sciences, Faculty of Life & Sciences & Medicine, King\u2019s College, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bams","family":"Abila","sequence":"additional","affiliation":[{"name":"School of Cancer & Pharmaceutical Sciences, Faculty of Life & Sciences & Medicine, King\u2019s College, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Mostafa Kamel","sequence":"additional","affiliation":[{"name":"School of Cancer & Pharmaceutical Sciences, Faculty of Life & Sciences & Medicine, King\u2019s College, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1158\/2159-8290.CD-12-0548","article-title":"The basic principles of chimeric antigen receptor design","volume":"3","author":"Sadelain","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_2","unstructured":"FDA (2022, December 13). 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