Use of HSP110 Peptide Binding Protein for Development of New Breast Cancer Vaccines

摘要

Several studies have shown that certain stress proteins can function as potent vaccines against a specific cancer when purified from the same tumor. We have hypothesized in our application that hsp 110 may be an excellent candidate for cancer vaccines. Here, we describe the studies of the vaccine potential of hsp 110 and its ER homologue grp 170, two long recognized but unstudied stress proteins. Vaccination with these two HSPs purified from Meth A fibrosarcoma caused the complete tumor regression. A significant growth inhibition of Colon 26 tumor was also seen in the immunized animals. HSP vaccination significantly extended the life span of tumor-bearing mice when applied after tumor transplantation and decreased experimental lung metastasis in a melanoma tumor model, A tumor specific CTL response developed in the mice immunized with tumor derived hsp 110 or grp 170. Antibody depletion assay demonstrated that NK cells in conjunction with CD4+ and CD8+ T cells were involved in the protective immunity elicited by HSP vaccination. Furthermore, treatments of the mice with bone marrow derived dendritic cells pulsed with hsp 110 or grp 170 fromtumor also elicited a strong anti-tumor response indicating that dendritic cells can be used to efficiently mediate this therapeutic approach. Additionally, we showed. that mild, fever-like hyperthermic conditions, which have been shown to stimulate other immunological functions, also stimulate the vaccine efficiency of hsp 110 as well as hsc 70, but not grp 170. Peptides profile stripped from tumor-derived hsp 110 was also. analyzed. We also extend our studies to the development of hsp 110 vaccines targeting breast tumor antigen. Immunization with ICD (intracellular domain of Her2/neu) complexed with hsp110 elicited antigen specific immune response. These studies indicate that these large stress proteins can be used in heat shock protein- based cancer immunotherapy.