HSP110-HER2/neu Chaperone Complex Vaccine Induces Protective Immunity Against Spontaneous Mammary Tumors in HER-2/neu Transgenic Mice
作者： Masoud H. Manjili , Xiang-Yang Wang , Xing Chen , Thomas Martin , Elizabeth A. Repasky
DOI: 10.4049/JIMMUNOL.171.8.4054
关键词: Immunotherapy 、 CD8 、 Mammary tumor 、 IL-2 receptor 、 Chaperone complex 、 Biology 、 Cancer research 、 Interleukin 21 、 Immune system 、 Molecular biology 、 HER2/neu 、 Immunology
摘要: Heat shock proteins (HSPs) are shown to be strong immunoadjuvants, eliciting both innate and adaptive immune responses against cancers. HSP110 is related in sequence HSP70 ∼4-fold more efficient binding stabilizing denatured protein substrates compared with HSP70. In the present study we evaluated ability of a heat complex intracellular domain (ICD) human HER-2/ neu elicit effective antitumor inhibit spontaneous mammary tumors FVB- (FVBN202) transgenic mice. The HSP110-ICD was capable breaking tolerance rat inhibiting tumor development. This vaccine induced ICD-specific IFN-γ IL-4 production. Depletion studies revealed that CD8 + T cells were involved protection challenge mouse tumors, whereas CD4 partial protection. Increased IgG2a Ab titer sera tumor-free animals after vaccination elevated CD25 regulatory PBL tumor-bearing suggested IFN-γ-producing Th1 may responsible for challenge, (Th2 cells) suppress responses. Together, these results suggest can up-regulation prevent complete eradication following immunotherapy.
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