Journal
CANCER GENE THERAPY
Volume 19, Issue 8, Pages 566-571Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2012.34
Keywords
Wilms' tumor gene; Epstein-Barr virus; bacterial artificial chromosome; lymphoblastoid cell line
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Ministry of Health Labour and Welfare
- NOASTEC (Northern Advancement Center for Science and Technology)
- Naito Foundation
- Grants-in-Aid for Scientific Research [23659489] Funding Source: KAKEN
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Lymphoblastoid cell lines (LCLs), which are established by in vitro infection of peripheral B-lymphocytes with Epstein-Barr virus (EBV), are effective antigen-presenting cells. However, the ability of LCLs to present transduced tumor antigens has not yet been evaluated in detail. We report a single-step strategy utilizing a recombinant EBV (maxi-EBV) to convert B-lymphocytes from any individuals into indefinitely growing LCLs expressing a transgene of interest. The strategy was successfully used to establish LCLs expressing Wilms' tumor gene 1 (WT1) tumor antigen (WT1-LCLs), which is an attractive target for cancer immunotherapy. The established WT1-LCLs expressed more abundant WT1 protein than K562 leukemic cells, which are known to overexpress WT1. A WT1-specific cytotoxic T lymphocyte line efficiently lysed the WT1-LCL in a human leukocyte antigen-restricted manner, but poorly lysed control LCL not expressing WT1. These results indicate that the transduced WT1 antigen is processed and presented on the WT1-LCL. This experimental strategy can be applied to establish LCLs expressing other tumor antigens and will find a broad range of applications in the field of cancer immunotherapy.
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