{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:43:48Z","timestamp":1792122228633,"version":"4.4.0"},"reference-count":184,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008730","name":"The Norwegian Cancer Society","doi-asserted-by":"crossref","award":["297210"],"award-info":[{"award-number":["297210"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond oncology, CAR-T cell therapy has also shown promise in autoimmune diseases, where early clinical studies suggest that B cell-directed CAR-T cells can induce sustained remission in conditions such as systemic lupus erythematosus. This review highlights advances in CAR-T cell engineering, including DNA- and mRNA-based platforms for ex vivo and in vivo programming, and discusses emerging strategies to enhance CAR-T cell trafficking, persistence, and resistance to TME.<\/jats:p>","DOI":"10.3390\/ijms27020909","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:39:37Z","timestamp":1768563577000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy"],"prefix":"10.3390","volume":"27","author":[{"given":"Mouldy","family":"Sioud","sequence":"first","affiliation":[{"name":"Division of Cancer Medicine, Department of Cancer Immunology, Oslo University Hospital\u2014Rdiumhospitalet, Ullernchausseen 70, 0379 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-8710","authenticated-orcid":false,"given":"Nicholas Paul","family":"Casey","sequence":"additional","affiliation":[{"name":"Division of Cancer Medicine, Department of Cancer Immunology, Oslo University Hospital\u2014Rdiumhospitalet, Ullernchausseen 70, 0379 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric Antigen Receptor Therapy","volume":"379","author":"June","year":"2018","journal-title":"N. 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