Immunotherapy with BiTE® Antibodies: Lessons Learned from Blinatumomab

T cell-engaging bispecific antibodies can transiently link with otherwise inactive cytotoxic T cells in patientsʼ tumor cells and induce redirected potent lysis of tumor cells. One example for this is blinatumomab (AMG 103), a CD19/-CD3-bispecific BiTE® antibody used to treat acute lymphocytic leukemia (ALL) and non-Hodgkinʼs lymphoma (NHL), which is in an advanced stage of clinical development. Two other BiTE® antibodies, AMG 211/MEDI-565 (CEA/CD3-specific) and AMG 110 (EpCAM/CD3-specific), are in the early stages of clinical development to treat solid tumors. Blinatumomab and all other BiTE® antibodies have been shown to activate T cells in a highly conditional manner that was strictly dependent on the presence of target cells, effect the serial lysis of target cells by T cells, induce T cell proliferation, and act at sub-nanomolar concentrations. The mode of action of BiTE® will be described in detail and compared to other treatment modalities.

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