Allergen specific antibody therapies

抗体疗法由于其高特异性和亲和力，是目前消除或操纵免疫细胞的最特异性的免疫学方法。因此，治疗性抗体的潜力取决于其Ig同型特异性Fc部分与免疫细胞上特异性抑制和激活Fc受体的相互作用。通过使用卵清蛋白（OVA）诱导的哮喘小鼠模型，我们希望建立过敏原特异性抗体疗法，i)在急性过敏反应期间抑制过敏原依赖性IgE活性和IgE产生，ii)在过敏反应之前或之间通过靶向树突状细胞诱导长期耐受性。我们希望通过将IgG抑制受体FcgammaRIIB与合成的过敏原特异性或过敏原偶联的IgG抗体（IgG1、IgG2a和IgG2b）交联，并通过额外阻断激活IgG Fcgamma受体，在过敏原特异性B细胞和IgE靶细胞（如肥大细胞、嗜碱性粒细胞和嗜酸性粒细胞）中诱导负信号，从而阻断急性过敏反应。此外，我们将分析合成的过敏原特异性和过敏原偶联IgM抗体的抑制潜力。这些研究将证明，哪个igfc部分在过敏反应中具有最高的抑制潜力。我们进一步想分析这些合成抗体的潜力，通过将过敏原靶向树突状细胞诱导调节性T细胞来产生长期耐受性。在另一种方法中，我们希望通过使用过敏原偶联的DEC-205或33D1抗体特异性地将过敏原靶向不同亚群的树突状细胞来诱导长期耐受性，这些抗体分别识别CD8+或CD8-树突状细胞表面的靶蛋白。在未来，开发的结果将转移到天然过敏原和人体系统。

Antibody therapies are currently the most specific immunological approaches to eliminate or manipulate immune cells because of their high specificity and affinity. The potential of therapeutic antibodies is thereby determined by the interaction of their Ig isotype specific Fc part with specific inhibitory and activating Fc receptors on immune cells. By using an ovalbumin (OVA) induced asthma mouse model we here want to establish allergen specific antibody therapies i) to inhibit allergen dependent IgE activity and IgE production during acute allergic reactions or ii) to induce long term tolerance before or between allergic reactions by targeting dendritic cells. We want to block acute allergic reactions by inducing a negative signal in allergen specific B cells and in IgE target cells like mast cells, basophils and eosinophils via crosslinking the IgG inhibitory receptor FcgammaRIIB with synthezised allergen specific or allergen coupled IgG antibodies (IgG1, IgG2a and IgG2b) and via additionally blocking activating IgG Fcgamma receptors. Additionally, we will analyze an inhibitory potential of synthesized allergen specific and allergen coupled IgM antibodies. These investigations will demonstrate, which Ig Fc part has the highest inhibitory potential in allergic reactions. We further want to analyze the potential of these synthesized antibodies to generate long term tolerance by targeting the allergen to dendritic cells to induce regulatory T cells. In another approach we want to induce long term tolerance by specifically targeting the allergen to different subsets of dendritic cells with allergen coupled DEC-205 or 33D1 antibodies, which recognize a target protein on the surface of CD8+ or CD8- dendritic cells, respectively. In the future, the developed results will be transferred to natural allergens and to the human system.