{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:35:21Z","timestamp":1781109321547,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,11]]},"abstract":"<jats:p>Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin containing the heavy and light variable regions of the anti-Tac monoclonal antibody fused to a mutant form of Pseudomonas exotoxin (PE). Anti-Tac binds to the p55 subunit of the human interleukin 2 (IL-2) receptor, and anti-Tac(Fv)-PE40 kills human or monkey cell lines that contain either the intact IL-2 receptor or its p55 subunit alone. To assess the usefulness of anti-Tac(Fv)-PE40 in treatment of IL-2 receptor-positive leukemia, we tested peripheral blood mononuclear cells from six patients with adult T-cell leukemia. In each of the six patients, anti-Tac(Fv)-PE40 was extremely cytotoxic to the malignant cells. Metabolic activity and sensitivity of the fresh cells improved when a small amount of IL-2 (10 units per ml) was present during incubation. The toxin concentration necessary to inhibit protein synthesis by 50% after 16-hr incubation of cells with immunotoxin varied from 1.6 to 16 ng\/ml (2.5-25 x 10(-11) M). In every case, binding was by means of the Tac antigen because anti-Tac(Fv)-PE40 cytotoxicity was prevented by adding excess anti-Tac antibody. Moreover, anti-Tac alone or an inactive mutant of anti-Tac(Fv)-PE40 without ADP-ribosylation activity had very little cytotoxic activity. Peripheral blood mononuclear cells from normal controls, from a patient with Tac-negative leukemia, and from adult T-cell leukemia patients without significant peripheral blood involvement were not sensitive to anti-Tac(Fv)-PE40. These results indicate that anti-Tac(Fv)-PE40 is a potent cytotoxin against adult T-cell leukemia cells in vitro and warrants clinical testing.<\/jats:p>","DOI":"10.1073\/pnas.87.21.8291","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:30:10Z","timestamp":1149060610000},"page":"8291-8295","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["The recombinant immunotoxin anti-Tac(Fv)-Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia."],"prefix":"10.1073","volume":"87","author":[{"given":"R J","family":"Kreitman","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V K","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M C","family":"Willingham","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Pastan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,11]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.21.8291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:14:18Z","timestamp":1649855658000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.21.8291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,11]]},"references-count":0,"journal-issue":{"issue":"21","published-print":{"date-parts":[[1990,11]]}},"alternative-id":["10.1073\/pnas.87.21.8291"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.21.8291","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,11]]},"assertion":[{"value":"1990-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}