METHODS AND COMPOSITIONS FOR IMMUNOTHERAPY AND DETECTION OF INFLAMMATORY AND IMMUNE-DYSREGULATORY DISEASE, INFECTIOUS DISEASE, PATHOLOGIC ANGIOGENESIS AND CANCER

摘要

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.