Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.
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.
Dudley
Mark E
ME
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20902, USA.
Wunderlich
John R
JR
Robbins
Paul F
PF
Yang
James C
JC
Hwu
Patrick
P
Schwartzentruber
Douglas J
DJ
Topalian
Suzanne L
SL
Sherry
Richard
R
Restifo
Nicholas P
NP
Hubicki
Amy M
AM
Robinson
Michael R
MR
Raffeld
Mark
M
Duray
Paul
P
Seipp
Claudia A
CA
Rogers-Freezer
Linda
L
Morton
Kathleen E
KE
Mavroukakis
Sharon A
SA
White
Donald E
DE
Rosenberg
Steven A
SA
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
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