Human heat shock protein-specific cytotoxic T lymphocytes display potent antitumour immunity in multiple myeloma.
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 that HSPs are highly expressed by most myeloma cells and vital to myeloma cell survival, we reasoned that HSPs themselves might be an ideal myeloma antigen. In the present study, we explored the feasibility of targeting HSPs themselves for treating multiple myeloma. We identified and chose HLA-A*0201-binding peptides from human HSPB1 (HSP27) and HSP90AA1 (HSP90), and confirmed their immunogenicity in HLA-A*0201 transgenic mice. Dendritic cells pulsed with HSPB1 and HSP90AA1 peptides were used to stimulate peripheral blood mononuclear cells from healthy volunteers and myeloma patients to generate HSP peptide-specific cytotoxic T lymphocytes (CTLs). HSP peptide-specific CTLs efficiently lysed HLA-A*0201(+) myeloma cells (established cell lines and primary plasma cells) but not HLA-A*0201(-) myeloma cells in vitro, indicating that myeloma cells naturally express HSP peptides in the context of major histocompatibility complex class I molecules. More importantly, HSP peptide-specific CTLs effectively reduced tumour burden in the xenograft mouse model of myeloma. Our study clearly demonstrated that HSPs might be novel tumour antigens for immunotherapy of myeloma.
Myeloma & Lymphoma Centre, Department of Haematology, Changzheng Hospital, Shanghai, China.
Rong
R
Li
Jianfei
J
Qian
Wenhao
W
Zhang
Weijun
W
Fu
Juan
J
Du
Hua
H
Jiang
Hui
H
Zhang
Chunyang
C
Zhang
Hao
H
Xi
Qing
Q
Yi
Jian
J
Hou
D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006360:Heat-Shock Proteins; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008875:Middle Aged; D018832:Molecular Chaperones; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D055551:HSP27 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C112969:HSP90AA1 protein, human; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments
heat shock proteins; immunotherapy; multiple myeloma; vaccine