{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:26:24Z","timestamp":1777962384339,"version":"3.51.4"},"reference-count":150,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulated real-world evidence and the barriers associated with applying clinical trials to clinical practices from the perspective of the quality and technical aspects. After providing an overview of all the moving parts involved in the production of CAR-T-cell products, we discuss the characteristics of immune cells (given that T cells are the raw materials for CAR-T-cell therapy) and elucidate the relationship between lifestyle, including diet and exercise, and immune cells. Finally, we briefly highlight future trends in the development of immune cell therapy. These advancements may help position CAR-T-cell therapy as a standard of care.<\/jats:p>","DOI":"10.3390\/ph15020207","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0991-9086","authenticated-orcid":false,"given":"Yuki","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Cell & Gene Therapy, Oncology, Novartis Pharma K.K., 1-23-1, Toranomon, Minato-ku, Tokyo 105-6333, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Kato","sequence":"additional","affiliation":[{"name":"Oncology Medical Affairs Dept, Novartis Pharma K.K., 1-23-1, Toranomon, Minato-ku, Tokyo 105-6333, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Futoshi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Oncology Medical Affairs Dept, Novartis Pharma K.K., 1-23-1, Toranomon, Minato-ku, Tokyo 105-6333, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-8889","authenticated-orcid":false,"given":"Muha","family":"Sunahara","sequence":"additional","affiliation":[{"name":"Oncology Medical Affairs Dept, Novartis Pharma K.K., 1-23-1, Toranomon, Minato-ku, Tokyo 105-6333, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshie","family":"Tsurumaki","sequence":"additional","affiliation":[{"name":"Cell & Gene Therapy, Oncology, Novartis Pharma K.K., 1-23-1, Toranomon, Minato-ku, Tokyo 105-6333, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-immunol-100311-102839","article-title":"Decisions about Dendritic Cells: Past, Present, and Future","volume":"30","author":"Steinman","year":"2012","journal-title":"Annu. 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