Viral specific cytotoxic T cells inhibit the growth of TfR-expressing tumor cells with antibody targeted viral peptide/HLA-A2 complex.
A fusion protein of single chain antibody (scFv) specific for transferrin receptor (TfR, CD71) and viral peptide/HLA-A2 complex was prepared in this study to redirect cytotoxic T cells (CTLs) of viral specificity to tumor cells by attaching the ligand of T cell receptor (TCR) to tumor cells via binding of TfR scFv to TfR. The results demonstrate that the fusion protein can attach the active virus-peptide/HLA-A2 complex to HLA class I-negative, TfR-expressing K562 cells through binding of TfR scFv to TfR, and mediate cytotoxicity of viral peptide-specific CTLs against K562 cells in vitro. In addition, the fusion protein can induce inhibition of solid tumor formation and improve survival time in tumor xenograft nude mouse with the injection of the sorted viral peptide-specific CTLs generated by co-culture of peripheral blood lymphocytes from HLA-A2 positive donors with inactivated T2 cells pulsed with the viral peptide.
Li
Jianan
J
Department of Immunology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Weng
Xiufang
X
Liang
Zhihui
Z
Zhong
Maohua
M
Chen
Xueling
X
Lu
Shengjun
S
Sun
Wei
W
Song
Yinhong
Y
Wu
Xiongwen
X
Shen
Guanxin
G
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D015789:HLA-A2 Antigen; D006801:Humans; D020014:K562 Cells; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000276:immunology*; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D011990:Receptors, Transferrin; D014760:Viral Fusion Proteins