Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes.
The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 -/-) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.
Vierboom
M P
MP
Department of Immunohematology and Blood Bank, University Hospital Leiden, 2300 RC Leiden, the Netherlands.
Nijman
H W
HW
Offringa
R
R
van der Voort
E I
EI
van Hall
T
T
van den Broek
L
L
Fleuren
G J
GJ
Kenemans
P
P
Kast
W M
WM
Melief
C J
CJ
D019264:Adoptive Transfer; D000818:Animals; D002470:Cell Survival; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D006651:Histocytochemistry; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53