{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T05:32:04Z","timestamp":1782192724265,"version":"3.54.5"},"reference-count":57,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:p>\n                    Chimeric antigen receptors (CARs) are artificial fusion proteins that incorporate antigen-recognition domains and T cell signaling domains. CD30 is a cell surface protein expressed on Hodgkin's lymphoma, some T cell lymphomas, and some B cell lymphomas. CD30 has a restricted expression pattern in normal cells, so CD30 has good potential as a clinical target for CAR T cells. We compared three different anti-CD30 CAR designs incorporating a single-chain variable fragment derived from the 5F11 fully human monoclonal antibody. 5F11-28Z has hinge, transmembrane, and costimulatory domains from CD28 and a CD3\u03b6 T cell activation domain. 5F11-CD828Z has hinge and transmembrane domains from CD8\u03b1, a CD28 costimulatory domain, and a CD3\u03b6 T cell activation domain. 5F11-CD8BBZ is identical to 5F11-CD828Z, except for the replacement of the CD28 moiety with a 4-1BB moiety. We found that T cells expressing 5F11-CD8BBZ had lower levels of CD30-specific degranulation and cytokine release compared with CD28-containing CARs. When compared to the CD28-containing CARs, T cells expressing 5F11-CD8BBZ had higher levels of nonspecific functional activity, including degranulation, cytokine release, and proliferation, when stimulated with CD30-negative target cells. We established tumors in nod-scid common gamma-chain deficient (NSG) mice and treated the tumors with T cells expressing different CARs. T cells expressing 5F11-28Z were most effective at eradicating tumors. T cells expressing 5F11-CD828Z had intermediate effectiveness, and T cells expressing 5F11-CD8BBZ were least effective. CD30\n                    <jats:sup>+<\/jats:sup>\n                    T cells are lost from cultures of T cells containing 5F11-28Z-expressing T cells. This indicated the killing of CD30\n                    <jats:sup>+<\/jats:sup>\n                    T cells by the 5F11-28Z-expressing T cells. Despite this, the number of T cells in the cultures consistently accumulated to numbers needed for use in a clinical trial. Based on all\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and murine experiments comparing the different CARs, we selected 5F11-28Z for further development, and we have initiated a clinical trial testing 5F11-28Z T cells.\n                  <\/jats:p>","DOI":"10.1089\/hum.2020.215","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:38:38Z","timestamp":1607395118000},"page":"730-743","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Design and Assessment of Novel Anti-CD30 Chimeric Antigen Receptors with Human Antigen-Recognition Domains"],"prefix":"10.1177","volume":"32","author":[{"given":"Stephanie","family":"Choi","sequence":"first","affiliation":[{"name":"National Institutes of Health, National Cancer Institute, Center for Cancer Research, Surgery Branch, Bethesda, Maryland, 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