Abstract
Molecular definition of cancer specific antigens recognized by T cells opened an approach to develop cancer specific immunotherapy. Through a series of key findings in cancer immunology, for development of effective therapy major effort has been directed to how to induce T cells with fine specificity, sufficient quantity and high quality in hosts. We intended to integrate immunobiological strategy of T cells with two technologies, nanogel technology and retroviral vector technology for translational research of cancer immunotherapy. Cholesterol-bearing hydrophobizedpullulan (CHP), physically cross-linked nanogels by self-assembly, form nanoparticle complex with protein in water.We found that antigen protein with multiple T cell epitopes, when complexed with CHP, was efficiently transported to lymph nodes and well captured by antigen presenting cells such as dendritic cells and macrophages leading to cross presentation. Hence, CHP-antigen protein complex may become excellent cancer vaccine to induce both CD8+ killer T cells and CD4+ helper T cells of high quality. Intrinsic weakness of insufficiency in number of cancer specific T cells in hosts, prompted us to develop adoptive T cell therapy with lymphocytes engineered to possess cancer specificity. For this purpose, we developed novel retroviral vectors to highly express exogenously transduced cancer specific T cell receptor (TCR), yet suppressing expression of endogenous polyclonal TCR. This approach allowed us to prepare T cells with finer specificity of expressed TCR. In addition, use of RetroNectin®, a recombinant fragment of fibronectin opened a way to ex vivo prepare T cells of sufficient quantity and good quality for clinical use. Translational clinical trials of these cancer vaccine and adoptive T cell therapy are now on-going. An open innovation to promote fusion of different fields of science and technology played an essential role in our development of cancer immunotherapy.
Highlights
Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases
tumor necrosis factor (TNF) therapy and demyelinating event: A report indicates that adverse events such as the demyelinating lesion in the brain, optic neuritis, and neuropathy occurred after treatment with anti-TNF alpha therapy in collagen disease, and TNF antagonizing therapy showed worsening in a clinical trial with MS
Believing on the similarities of normal joints in humans and monkeys, we have employed a model of collagen-induced arthritis in Macaca fascicularis in an attempt to evaluate the histological alterations caused by such condition in the extracellular matrix of the articular cartilage
Summary
Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases. Acute Serum Amyloid A (A-SAA) is an acute phase protein strongly expressed in rheumatoid arthritis (RA) synovial tissue (ST) critically involved in regulating cell migration and angiogenesis These processes are dependent on downstream interactions between extracellular matrix and cytoskeletal components. Conclusions: These results indicate that Egr-1 contributes to IL-1mediated down-regulation of PPARg expression in OA chondrocytes and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases. Immune cell-derived microparticles (MPs) are present at increased amounts in synovial fluid of rheumatoid arthritis (RA) patients [1] and can activate disease-relevant signalling pathways in RA synovial fibroblasts (SF) [2,3].
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