SV40 Tag-specific cytotoxic T lymphocytes generated from the peripheral blood of malignant pleural mesothelioma patients.
Malignant pleural mesothelioma (MPM) is an aggressive cancer, with survival of less than one year following diagnosis and treatment with current protocols. Recent studies have demonstrated the presence of the simian virus 40 (SV40)-like, large tumor antigen (Tag) in nearly 60% of MPMs. SV40 Tag is a viral-encoded tumor-specific antigen, and thus a potential target for the induction of anti-tumor immunity and the development of therapeutic vaccines. We describe here evidence for the existence of SV40 Tag-specific immune responses in patients with MPM whose tumors express Tag. Humoral immunity was demonstrated by the detection of IgG titers against Tag in serum samples from 1/3 of patients examined. CTLs were generated from the peripheral blood of an HLA-A2(+) MPM patient with a synthetic peptide representing an HLA-A2 binding epitope in SV40 Tag. The CTLs demonstrated epitope fine specificity, in that other peptides from SV40 Tag and a peptide from influenza virus were not recognized in the context of HLA-A2. Moreover, the CTLs were capable of recognizing mesothelioma tumor cells that expressed SV40 Tag, in an MHC class I restricted manner.
Bright
Robert K
RK
Laboratory of Prostate Cancer Biology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, and the Oregon Cancer Center, 4805 NE Glisan Street, Portland, OR 97213, USA. rbright@providence.org
Kimchi
Eric T
ET
Shearer
Michael H
MH
Kennedy
Ronald C
RC
Pass
Harvey I
HI
D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D016056:Immunodominant Epitopes; D008654:Mesothelioma / Q000276:immunology*; D010997:Pleural Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes