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Allo‐restricted CTLs generated by coculturing of PBLs and autologous monocytes loaded with allogeneic peptide/HLA/IgG1‐Fc fusion protein
Author(s) -
Weng Xiufang,
Lu Shengjun,
Zhong Maohua,
Liang Zhihui,
Shen Guanxin,
Chen Jianguo,
Wu Xiongwen
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0408242
Subject(s) - epitope , cytotoxic t cell , cd8 , biology , immunology , human leukocyte antigen , microbiology and biotechnology , antigen , immunotherapy , cancer research , virology , immune system , biochemistry , in vitro
The graft‐versus‐leukemia effect of allogeneic marrow transplantation suggests the dramatic effect of the allogeneic T cell to eradicate malignant disease. Preparation and adoptive transfusion of tumor‐specific T cells from HLA‐mismatched donors might be expected to circumvent CTL tolerance to the tumor. In this study, a soluble, divalent HLA‐A2 molecule was constructed with the Fc part of human IgG1 and was pulsed with a peptide related to melanoma tyrosinase 368–376 [Tyr 368–376 (Tyr)] to form the Tyr/HLA‐A2 dimer, which allowed loading onto monocytes via interaction of the Fc and FcR. The HLA‐A2‐negative (HLA‐A2‐ve) monocytes loaded with the Tyr/HLA‐A2 dimer acted as allo‐APC with copies of a single allogeneic epitope. After coculture of the HLA‐A2‐ve PBLs and autologous monocytes loaded with the dimer, CD8+ cells in the coculture show an obvious proliferation and increased frequency of Tyr/HLA‐A2 tetramer‐stained cells. The sorted Tyr/HLA‐A2 tetramer‐positive CD8+ cells display an elevated cytotoxic activity against HLA‐A2‐positive melanoma cells expressing tyrosinase endogenously (i.e., SK‐Mel‐5) but little against tyrosinase‐negative melanoma cells (i.e., A375). The coculture of PBLs and autologous monocytes loaded with allogeneic peptide/HLA complexes offers a novel approach to expand allo‐restricted, peptide‐specific CTLs, which might be a potential arsenal for treatment of patients with malignant disease, if the tumor‐related epitope were defined.