Oct, 2008
Cyclin D1-Specific Cytotoxic T Lymphocytes Are Present in the Repertoire of Cancer Patients: Implications for Cancer Immunotherapy
CLINICAL CANCER RESEARCH
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- Volume
- 14
- Number
- 20
- First page
- 6574
- Last page
- 6579
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1158/1078-0432.CCR-08-0825
- Publisher
- AMER ASSOC CANCER RESEARCH
Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1 derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells.
Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay.
Results: After screening, at least two naturally processed and presented HLA-A*0201 - binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201 - matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer.
Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.
Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay.
Results: After screening, at least two naturally processed and presented HLA-A*0201 - binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201 - matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer.
Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.
- Link information
-
- DOI
- https://doi.org/10.1158/1078-0432.CCR-08-0825
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000260359600027&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-58149199123&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0003-0995-9405
- ID information
-
- DOI : 10.1158/1078-0432.CCR-08-0825
- ISSN : 1078-0432
- ORCID - Put Code : 47323608
- SCOPUS ID : 58149199123
- Web of Science ID : WOS:000260359600027