title: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.
abstract: We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20902, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Schwartzentruber
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Richard
authors.initials: R
authors.lastname: Sherry
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Amy M
authors.initials: AM
authors.lastname: Hubicki
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Paul
authors.initials: P
authors.lastname: Duray
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Seipp
authors.forename: Linda
authors.initials: L
authors.lastname: Rogers-Freezer
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Morton
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Mavroukakis
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta