Cancer immunotherapy attempts to exploit the capability of the immune system to attack malignant cells. Recent results suggest that clinical responses in patients point to this new mechanism as potentially beneficial in harnessing the immune system for combating established malignancies. These checkpoint-related immunotherapies rely on engaging a subset of T cells in anti-tumor immune responses. BiTE® (Bi-specific T cell engager) represents a distinct modality that directly engages any T cell and a specific antigen expressing tumor cell. The approach offers the advantage of engaging T cells and patient tumor cells that differentially express a specific cell surface antigen. The specificity confers redirected tumor cell killing and recent clinical data with the BiTE blinatumomab show evidence of clinical remissions. The characteristics of a suitable BiTE with the benefit of CD3 mediated T cell recognition and articulation of tumor specific antigens combined in this therapeutic modality is described here.