title: Cancer regression in patients after transfer of genetically engineered lymphocytes.
abstract: Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Richard E
authors.initials: RE
authors.lastname: Royal
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zheng
authors.forename: Azam
authors.initials: A
authors.lastname: Nahvi
authors.forename: Christiaan R
authors.initials: CR
authors.lastname: de Vries
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Rogers-Freezer
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Mavroukakis
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use; D002478:Cells, Cultured; D018274:Electroporation; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta