Human heat shock protein-specific cytotoxic T lymphocytes display potent antitumour immunity in multiple myeloma

• DOI: 10.1111/bjh.12943
• Publication Date: 2014-05-14T06:45:18Z
• Authors: Rong Li; Jianfei Qian; Wenhao Zhang; Weijun Fu; Juan Du; Hua Jiang; Hui Zhang; Chunyang Zhang; Hao Xi; Qing Yi; Jian Hou
• Keywords: Male; 0301 basic medicine; HSP27 Heat-Shock Proteins; Mice, Transgenic; Mice, SCID; Middle Aged; Immunotherapy, Adoptive; Peptide Fragments; 3. Good health; Mice; 03 medical and health sciences; Mice, Inbred NOD; Cell Line, Tumor; HLA-A2 Antigen; Animals; Humans; Female; HSP90 Heat-Shock Proteins; Multiple Myeloma; Heat-Shock Proteins; Aged; Molecular Chaperones; T-Lymphocytes, Cytotoxic

Tumour cell-derived heat shock proteins (HSPs) are used as vaccines for immunotherapy of cancer patients. However, it is proposed that the peptide chaperoned on HSPs, not HSPs themselves, elicited a potent immune response. Given highly expressed by most myeloma cells and vital to cell survival, we reasoned themselves might be an ideal antigen. In present study, explored feasibility targeting treating multiple myeloma. We identified chose HLA-A*0201-binding peptides from human HSPB1 (HSP27) HSP90AA1 (HSP90), confirmed their immunogenicity in HLA-A*0201 transgenic mice. Dendritic pulsed with were stimulate peripheral blood mononuclear healthy volunteers patients generate HSP peptide-specific cytotoxic T lymphocytes (CTLs). CTLs efficiently lysed HLA-A*0201(+) (established lines primary plasma cells) but HLA-A*0201(-) vitro, indicating naturally express context major histocompatibility complex class I molecules. More importantly, effectively reduced tumour burden xenograft mouse model Our study clearly demonstrated novel antigens