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.