Cancer regression in patients after transfer of genetically engineered lymphocytes.
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.
Morgan
Richard A
RA
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Dudley
Mark E
ME
Wunderlich
John R
JR
Hughes
Marybeth S
MS
Yang
James C
JC
Sherry
Richard M
RM
Royal
Richard E
RE
Topalian
Suzanne L
SL
Kammula
Udai S
US
Restifo
Nicholas P
NP
Zheng
Zhili
Z
Nahvi
Azam
A
de Vries
Christiaan R
CR
Rogers-Freezer
Linda J
LJ
Mavroukakis
Sharon A
SA
Rosenberg
Steven A
SA
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
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