Generating renal cancer-reactive T cells using dendritic cells (DCs) to present autologous tumor.
Dendritic cells (DCs) have been used as professional antigen-presenting cells in vitro to prime T-cell responses. In this study, we generated both CD8+ and CD4+ renal cell carcinoma (RCC)-reactive T cells using a completely autologous system of DCs presenting engulfed whole-tumor cells. We compared DCs presenting RCC tumor cells in different preparations and found ultraviolet-irradiated apoptotic tumor cells to be more immunogenic than necrotic tumor cells or live untreated tumor cells in generating tumor-reactive T cells. In analyzing the T cells generated in this fashion, a CD8+ RCC-reactive T-cell clone generated from a patient recognized an epitope derived from fibroblast growth factor 5 in the context of human leukocyte antigen (HLA) B44*02. CD4+ T cells generated from another patient recognized multiple allogeneic RCC lines expressing HLA-DRbeta1*04, indicating a common shared tumor antigen presented by HLA-DRbeta1*04. The technique of using DCs to present whole-tumor cells can consistently generate both CD4+ and CD8+ RCC-reactive T cells for use in both antigen identification and therapeutic protocols.
Wang
Qiong J
QJ
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hanada
Ken-ichi
K
Perry-Lalley
Donna
D
Bettinotti
Maria P
MP
Karpova
Tatiana
T
Khong
Hung T
HT
Yang
James C
JC
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D009336:Necrosis; D014466:Ultraviolet Rays
D000951:Antigens, Neoplasm; D018950:Lipopolysaccharide Receptors