{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:38:28Z","timestamp":1781105908467,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,8,16]]},"abstract":"<jats:p>Adoptive cellular immunotherapy, infusions of interleukin 2 (IL-2) in conjunction with in vitro-activated killer cells, has brought new hope to patients with cancer. The broad application of this strategy, however, is constrained by the need for repeated leukapheresis and by the labor-intensive process of in vitro activation of cells. Also, current protocols generally use nonphysiological and toxic concentrations of IL-2. Identification of an in vivo stimulant that renders T cells responsive to physiologic concentrations of IL-2 represents a potential improvement over existing approaches. We have determined whether in vivo administration of monoclonal antibodies (mAbs) directed at the T-cell surface protein CD3 induces T-cell responsiveness to IL-2, stimulates cytolytic molecular programs of natural killer cells and cytotoxic T cells, and induces tumor regression. These hypotheses were explored in a murine hepatic MCA-102 fibrosarcoma model. We report that in vivo administration of anti-CD3 mAbs plus IL-2 results in intrahepatic expression of mRNA-encoding perforin, cytotoxic T-cell-specific serine esterase, and tumor necrosis factor alpha. Anti-CD3 mAbs alone or IL-2 alone failed to induce or induced minimal expression of these molecular mediators of cytotoxicity. The anti-CD3 mAbs plus IL-2 regimen also resulted in a significantly smaller number of hepatic metastases and a significantly longer survival time of tumor-bearing mice, compared to treatment with anti-CD3 mAbs alone or IL-2 alone. Our findings suggest that a regimen of anti-CD3 mAbs plus IL-2 is a more effective antitumor regimen compared with anti-CD3 mAbs alone or IL-2 alone and advance an alternative immunotherapy strategy of potential value for the treatment of cancer in humans.<\/jats:p>","DOI":"10.1073\/pnas.91.17.7889","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:52:13Z","timestamp":1149065533000},"page":"7889-7893","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression."],"prefix":"10.1073","volume":"91","author":[{"given":"F","family":"Nakajima","sequence":"first","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Khanna","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Xu","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Lagman","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Haschemeyer","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Mouradian","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Wang","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K H","family":"Stenzel","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A L","family":"Rubin","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Suthanthiran","sequence":"additional","affiliation":[{"name":"Rogosin Institute, Department of Biochemistry, New York Hospital-Cornell Medical Center, NY 10021."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,8,16]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.17.7889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:50:37Z","timestamp":1649857837000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.17.7889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,8,16]]},"references-count":0,"journal-issue":{"issue":"17","published-print":{"date-parts":[[1994,8,16]]}},"alternative-id":["10.1073\/pnas.91.17.7889"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.17.7889","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,8,16]]},"assertion":[{"value":"1994-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}