HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system.
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.
Division of Virology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan. tkanda@aichi-cc.jp
T
T
Kanda
T
T
Ochi
H
H
Fujiwara
M
M
Yasukawa
S
S
Okamoto
J
J
Mineno
K
K
Kuzushima
T
T
Tsurumi
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D004854:Herpesvirus 4, Human; D006801:Humans; D007167:Immunotherapy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D011994:Recombinant Proteins; D025721:WT1 Proteins