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

Rong Li, Jianfei Qian, Wenhao Zhang, Weijun Fu, Juan Du, Hua Jiang, Hui Zhang, Chunyang Zhang, Hao Xi, Qing Yi, Jian Hou

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)690-701
Number of pages12
JournalBritish Journal of Haematology
Volume166
Issue number5
DOIs
StatePublished - Sep 2014

Keywords

  • Heat shock proteins
  • Immunotherapy
  • Multiple myeloma
  • Vaccine

ASJC Scopus subject areas

  • Hematology

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