Allo‐restricted CTLs generated by coculturing of PBLs and autologous monocytes loaded with allogeneic peptide/HLA/IgG1‐Fc fusion protein

作者: Xiufang Weng , Shengjun Lu , Maohua Zhong , Zhihui Liang , Guanxin Shen

DOI: 10.1189/JLB.0408242

关键词:

摘要: The graft-versus-leukemia effect of allogeneic marrow transplantation suggests the dramatic T cell to eradicate malignant disease. Preparation and adoptive transfusion tumor-specific cells from HLA-mismatched donors might be expected circumvent CTL tolerance tumor. In this study, a soluble, divalent HLA-A2 molecule was constructed with Fc part human IgG pulsed peptide related melanoma tyrosinase 368-376 (Tyr (Tyr)] form Tyr/HLA-A2 dimer, which allowed loading onto monocytes via interaction FcR. HLA-A2-negative (HLA-A2-ve) loaded Tyr/ dimer acted as allo-APC copies single epitope. After coculture HLA-A2-ve PBLs autologous CD8+ in show an obvious proliferation increased frequency tetramer-stained cells. sorted tetramer-positive display elevated cytotoxic activity against HLA-A2-positive expressing endogenously (i.e., SK-Mel-5) but little tyrosinase-negative A375). peptide/HLA complexes offers novel approach expand allo-restricted, peptide-specific CTLs, potential arsenal for treatment patients disease, if tumor-related epitope were defined.

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