Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo.
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.
Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
Bangqing
B
Yuan
Ronghua
R
Xian
Xianqu
X
Wu
Junjie
J
Jing
Kangning
K
Chen
Guojun
G
Liu
Zhenhua
Z
Zhou
D000818:Animals; D016367:Baculoviridae; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006358:Hot Temperature; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C117093:Zbtb7a protein, mouse; C098410:glucose-regulated protein 170