Human lung cancer cells endogenously expressing mutant p53 process and present the mutant epitope and are lysed by mutant-specific cytotoxic T lymphocytes.
The p53 oncoprotein frequently contains somatically acquired missense mutations and is often overexpressed in cancer cells. Missense mutations can give rise to new tumor-specific peptide sequences, which can act as targets for T-cell-mediated immunotherapy. To investigate the ability of human lung cancer cells to adequately process and present a mutant p53-derived CTL epitope, we transfected the human cell line HMy-2.C1R and the p53-null human lung cancer cell lines H358 and H1299 with an expression vector containing a human mutant p53 (135 Cys to Tyr). After transfection with the Kd restriction element, these cells were tested as targets for murine mutation-specific CTLs. We show that these human lung cancer cells effectively process and present this endogenous mutant human p53 epitope, resulting in efficient, mutant epitope-specific lysis by CTLs. In the presence of the appropriate restriction element, human lung cancer cells can be effectively targeted by CTLs specific for somatically acquired, endogenous mutant epitopes, supporting targeted immunotherapy efforts in lung cancer.
Ciernik
I F
IF
Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Berzofsky
J A
JA
Carbone
D P
DP
D000818:Animals; D000939:Epitopes; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D016159:Tumor Suppressor Protein p53