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Targeting antigens expressed by tumors in their micro environment was evaluated in a multi step process that focused on patients with non small cell lung cancer or prostate MAPK 活性化 cancer who received autologous tumor vaccines. Protein arrays were used to detect the difference in pre and post treatment antibody responses. Since autologous tumor was not available for most patients, gene expression profiles of established cell lines were used. Studies with NSCLC patients exhibiting a CR or stable disease found a common pat tern of antibody responses against antigens that were shared by the 13 NSCLC cell lines, Next IHC ana lysis of normal and lung cancer tissue specimens from tis sue arrays were evaluated for expression of the proteins identified as targets of a post vaccine antibody response.
br<> For a panel of three antigens studied, malignant tissue, but not normal tissue, stained strongly positive for expression of markers tested. These data argue that the ProtoArray technology can be used to assess antibody responses against MK-1775 targets relevant to cancer immunotherapy. Next a novel immunotherapy strategy employing autophagosome vaccines that contain defective ribosomal products and short lived proteins was reviewed. DRiPs and SLiPs are the center of MHC class I antigen processing pathway, and link the immunosur veillance of viruses and tumors. DRiPs enable the immune system to rapidly detect alterations in cellular gene expres sion with great sensitivity.
br<> DRiPS and SLiPS are rapidly degraded by proteasome, MS-275 HDAC 阻害剤 transported to the endoplasmic reticulum, bound by MHC Class I and transferred to the cell surface where they are postulated to contribute the majority of peptides decorating the surface of tumor cells. Proteosome blockade shunts DRiPS and SLiPS to the au tophagy pathway and by blocking a degradative step, autophagosomes can be harvested and used as a vaccine. In preclinical studies, an autophagosome vaccine was more therapeutic than a Gold Standard GVAX Vaccine in a 3 day established 3LL tumor model. Additional stud ies documented that autophagosomes from one unique sarcoma can prime an immune responses against other in dependently derived syngeneic sarcomas and can provide a significant level of protective immunity in 8 of 9 tumor combinations tested.
br<> In contrast, whole tumor cell vaccines only pro vided protection from a tumor challenge when the chal lenge was identical to the tumor used as a vaccine, These findings broke a paradigm with chemically induced sarcomas that had stood for more than 50 years. As such we consider it to be a promising strategy to move into pa tients. Thus, an Autophagosome Cancer Vaccine derived from two human cancer cell lines, one of mixed squa mous adenocarcinoma and another adenocarcinoma, was developed. This vaccine contains at least six of the tumor antigens prioritized by NCI, agonists for TLR 2, 3, 4, 7 and 9 as well as HSPs. An NCI funded randomized multi center phase II trial of cyclophosphamide with allogeneic non small cell lung cancer DRibble vaccine alone or with Granulocyte Macrophage Colony Stimulating Factor or Imiquimod for Adjuvant Treatment of Definitively Treated Stage IIIA or IIIB NSCLC will start in early 2013.