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We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A\n                    <jats:sup>*<\/jats:sup>\n                    0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209\u2013217(210M) and gp100:280\u2013288(288V). This blockade of CTLA-4 induced grade III\/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to \u201cself\u201d antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1533209100","type":"journal-article","created":{"date-parts":[[2003,7,8]],"date-time":"2003-07-08T15:18:15Z","timestamp":1057677495000},"page":"8372-8377","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1307,"title":["Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma"],"prefix":"10.1073","volume":"100","author":[{"given":"Giao Q.","family":"Phan","sequence":"first","affiliation":[{"name":"Surgery Branch, Laboratory of Pathology, and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; 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