Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo

Bangqing Yuan; Ronghua Xian; Xianqu Wu; Junjie Jing; Kangning Chen; Guojun Liu; Zhenhua Zhou

doi:10.1016/j.imbio.2012.01.006

Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo

Immunobiology. 2012 Jul;217(7):738-42. doi: 10.1016/j.imbio.2012.01.006. Epub 2012 Jan 10.

Authors

Bangqing Yuan¹, Ronghua Xian, Xianqu Wu, Junjie Jing, Kangning Chen, Guojun Liu, Zhenhua Zhou

Affiliation

¹ Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.

PMID: 22317751
DOI: 10.1016/j.imbio.2012.01.006

Abstract

Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170-Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170-Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Baculoviridae
Cancer Vaccines / administration & dosage
Cancer Vaccines / immunology*
Carcinoma, Lewis Lung / immunology
Carcinoma, Lewis Lung / mortality
Carcinoma, Lewis Lung / pathology
Carcinoma, Lewis Lung / prevention & control*
Cytotoxicity, Immunologic*
DNA-Binding Proteins / administration & dosage
DNA-Binding Proteins / genetics
DNA-Binding Proteins / immunology*
Endoplasmic Reticulum / genetics
Endoplasmic Reticulum / immunology
Enzyme-Linked Immunospot Assay
Glycoproteins / administration & dosage
Glycoproteins / genetics
Glycoproteins / immunology*
HSP70 Heat-Shock Proteins / administration & dosage
HSP70 Heat-Shock Proteins / genetics
HSP70 Heat-Shock Proteins / immunology*
Hot Temperature
Immunization
Lymphocyte Activation / immunology
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Protein Binding
Recombinant Proteins / administration & dosage
Recombinant Proteins / genetics
Recombinant Proteins / immunology
Survival Rate
T-Lymphocytes, Cytotoxic / immunology
T-Lymphocytes, Cytotoxic / metabolism
Transcription Factors / administration & dosage
Transcription Factors / genetics
Transcription Factors / immunology*
Tumor Burden / drug effects
Tumor Burden / immunology

Substances

Cancer Vaccines
DNA-Binding Proteins
Glycoproteins
HSP70 Heat-Shock Proteins
Recombinant Proteins
Transcription Factors
Zbtb7a protein, mouse
glucose-regulated protein 170