WANG Xu1, ZENG Dachuan1, ZHENG Renren1, HUANG Zhenglan1, GAO Miao2*
BCR-ABL is a specific cytoplasmic antigen of chronic myeloid leukemia, which is suitable to be a target for immunotherapy. In this study, the two antigen peptides, SSKALQRPV (SS) and GFKQSSKAL (GF), at the BCR-ABL fusion site were selected as targets. SS and GF were respectively fused with CTP (cytoplasmic transduction peptide). The fusion peptides were used to sensitize bone marrow-derived dendritic cells of Balb/c mouse. Under the mediation of cytoplasmic transduction peptide, CTP-SS and CTP-GF peptides smoothly entered the cytoplasm of dendritic cells and located in the endoplasmic reticulum, thus having the basic conditions to be recognized as endogenous antigens and be presented to the cell surface by MHC I molecules. In vitro culture, the spleen CD8+ T lymphocytes were stimulated by dendritic cells sensitized with CTP-SS or CTP-GF to obtain cytotoxic T lymphocytes against chronic myelogenous leukemia cells. Then, the effect of cytotoxic T lymphocytes against CML cells in vitro was tested. The results confirmed that dendritic cells loaded with CTP-GF antigen peptide could induce the proliferation and activation of CD8+ T lymphocytes and produce cytotoxic killing effects against CML cells. Therefore, the GF antigen peptide at the BCR-ABL fusion site is expected to be a well target for CML immunotherapy. This study prepares the conditions for identifying specific TCR sequences on the surface of T lymphocytes that target CML cells, and then lays the foundation for our subsequent preparation of TCR-T cells that target CML.
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