Eradication of established tumors by CD8+ T cell adoptive immunotherapy.
We generated the DUC18 T cell receptor transgenic mouse expressing an H-2Kd -restricted transgenic T cell receptor specific for the syngeneic CMS5 fibrosarcoma rejection antigen mutated ERK2(136-144). DUC18 mice were capable of specifically eliminating lethal CMS5 tumor challenges, and transfer of DUC18 splenocytes to naive nontransgenic recipients conferred protection from subsequent and established CMS5 tumor burdens. Eradication of established tumor burdens by adoptive transfer of DUC18 splenocytes was dose and time dependent. Transferred tumor-specific T cells remained functional in vivo and capable of rejecting small tumors even in the presence of large, established tumor burdens. These findings highlight the kinetic battle between tumor growth and the production of a tumor-specific response and have critical implications for effective adoptive immunotherapy.
Hanson
H L
HL
Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Donermeyer
D L
DL
Ikeda
H
H
White
J M
JM
Shankaran
V
V
Old
L J
LJ
Shiku
H
H
Schreiber
R D
RD
Allen
P M
PM
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D005354:Fibrosarcoma / Q000276:immunology* / Q000628:therapy; D016219:Immunotherapy, Adoptive; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell