Therapeutic Antibodies in Stroke

Immunotherapy represents an active area of biomedical research to treat cancer, autoimmune diseases, and neurodegenerative disorders. In stroke, recanalization therapy is effective in reducing brain tissue damage after acute ischemic stroke. However, the narrow time window restricts its application for the majority of stroke patients. There is an urgent need to develop adjuvant therapies such as immunotherapy, stem cell replacement, and neuroprotective drugs. A number of molecules have been targeted for immunotherapy in stroke management, including myelin-associated proteins and their receptors, N-methyl-d-aspartic acid receptors, cytokines, and cell adhesion molecules. Both active vaccination and passive antibodies were tested in animal models of acute ischemic stroke. However, the mechanisms underlying the efficacy of immunotherapy are different for each target protein. Blocking myelin-associated proteins may enhance neuroplasticity, whereas blocking adhesion molecules may yield neuroprotection by suppressing the immune response after stroke. Although results from animal studies are encouraging, clinical trials using therapeutic antibodies failed to improve stroke outcome due to severe side effects. It remains a challenge to generate specific therapeutic antibodies with minimal side effects on other organs and systems.