A T cell receptor associated with naturally occurring human tumor immunity Journal Article
| Authors: | Santomasso, B. D.; Roberts, W. K.; Thomas, A.; Williams, T.; Blachere, N. E.; Dudley, M. E.; Houghton, A. N.; Posner, J. B.; Darnell, R. B. |
| Article Title: | A T cell receptor associated with naturally occurring human tumor immunity |
| Abstract: | The onconeural antigens appear to serve as tumor rejection antigens in the paraneoplastic neurologic disorders. Here, we used an unbiased peptide binding screen, followed by studies in HLA-A2.1 transgenic mice to identify naturally processed HLA-A2.1 restricted epitopes of the paraneoplastic cerebellar degeneration breast/ovarian cancer antigen cdr2. These mice were used to clone high-avidity cdr2-specific CD8+ T cells that recognize human tumor cells presenting endogenously loaded MHC class I-cdr2 peptide. T cells with this specificity were detected in the peripheral blood of two HLA-A2.1+ paraneoplastic cerebellar degeneration patients. We cloned T cell receptor (TCR) α and β genes from cdr2-specific T cells; electroporation of RNA encoding this TCR turned nonreactive donor T cells into efficient killers of human cdr2-expressing tumor cells. Cloned cdr2-specific TCR genes provide a clinically relevant means for immunologic targeting of human gynecologic cancers. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: | controlled study; aged; middle aged; unclassified drug; human cell; binding affinity; cd8+ t lymphocyte; cd8-positive t-lymphocytes; ovarian neoplasms; animals; mice; mus; ovary cancer; breast cancer; nerve tissue proteins; cell line, tumor; breast neoplasms; tumor antigen; mus musculus; mice, transgenic; molecular cloning; t lymphocyte receptor; t lymphocyte receptor beta chain; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; epitope; tumor cell; gene therapy; tumor immunity; cytotoxicity, immunologic; sequence homology; enzyme linked immunospot assay; gynecologic cancer; receptors, antigen, t-cell, alpha-beta; major histocompatibility antigen class 1; paraneoplastic neuropathy; hla a2 antigen; hla-a2 antigen; t lymphocyte receptor alpha chain; paraneoplastic cerebellar degeneration; immunity, natural; cerebellar degeneration related protein 2 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 104 |
| Issue: | 48 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2007-11-27 |
| Start Page: | 19073 |
| End Page: | 19078 |
| Language: | English |
| DOI: | 10.1073/pnas.0704336104 |
| PUBMED: | 18045792 |
| PROVIDER: | scopus |
| PMCID: | PMC2141910 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
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