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31 Harnessing autoimmunity (disease-specific autoantibody and its variant) in theranostics of disease
  1. E Matsuura1
  1. 1Okayama University, Collaborative Research Centre and Department of Cell Chemistry, Okayama, Japan

Abstract

The prevalence of autoimmune disorder or disease is characterised by its targeting autoantibodies. The term “theranostic”, an innovative concept of medical modality featuring a portmanteau of therapeutic and diagnostic systems, was coined in 2002 and has since undergone progressive development into current preclinical stages. Recently, we have prepared humanised and shortened variants of IgG (single chain variable fragment; 25 kDa-scFv) targeting towards: (i) β2-glycoprotein I (β2-GPI) complexed with oxidised LDL, a key population of pathogenic autoantibodies related to the development of antiphospholipid syndrome (APS) and autoimmune mediated atherosclerosis, and (ii) mesothelin, a 40 kDa-tumour differentiation antigen, to establish a clinically applicable theranostic in autoimmune mediated atherosclerosis and oncology. Goals of our theranostic system (comprises of novel and biodegradable 89Zr-radiolabeled nanoparticles conjugated with specific scFv) are to successfully deliver therapeutically effective small interfering RNA (siRNA), for inducing apoptosis in targeted cells of experimental models and to offer simultaneous visualisation of the targets via PET imaging system. The combination of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) and photo-controlled intracellular siRNA delivery system further offers a promising theranostic-based system in oncology, ideally via its targeted apoptosis-inducing feature. Alternatively, we have also proposed the combination of our novel theranostic system with alternative therapeutic candidates such domain I and proteolytic resistant domain V of β2-GPI, in combination with both PET imaging and metabonomics, as another feasible theranostic approach for management of angiogenesis-mediated cardiovascular disease (CVD) and cancer developments.

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