Human antibodies with anti-lymphocyte specificities and lytic activity
Antibody therapies that target human B cells are a promising way to treat diseases like B-cell cancers and autoimmune conditions like lupus and multiple sclerosis. Traditionally, these antibodies are made in animals and modified to resemble human antibodies to reduce immune rejection. Researchers in the Laboratory of Immunoregulation (LIR) at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a new approach of using blood plasma from a patient with the rare immune disorder idiopathic CD4 lymphocytopenia (ICL) to find naturally occurring human antibodies.
By using advanced genetic sequencing, the researchers discovered and reproduced several new antibodies that could effectively attack and kill B-cell tumors, normal B cells, and T cells, demonstrating potential for eliminating cancerous or disease-causing immune cells. One potent antibody, NIH58.9, killed B cells at low concentrations of 0.01 nanomolar. These new antibodies may be used as treatments, combined with other therapies, or engineered into special formats like bispecific antibodies or antibody-drug conjugates.
- Development of monoclonal antibody therapies, bispecific antibodies, and antibody-targeted drugs for use in organ transplantation, B-cell lymphomas, and autoimmune conditions
- First fully human IgM antibody that binds to and kills B cells
- Fully human monoclonal antibodies eliminating humanization steps associated with antibodies derived from animal models and lowering risk of anti-drug antibody response
- B-cell death observed at concentrations as low as 0.01Nm
- Versatile antibody that may be used directly, engineered as IgG1 antibody, and possibly developed into bispecifics or antibody-drug conjugates