부산대학교 도서관

SUMMARY:: Bispecific T-cell engager (BiTE) antibody constructs represent a novel immunotherapy that bridges cytotoxic T cells to tumor cells, thereby inducing target cell-dependent polyclonal T-cell activation and proliferation, and leading to apoptosis of bound tumor cells. Anti-CD19 BiTE blinatumomab has demonstrated clinical activity in Philadelphia chromosome (Ph)-negative relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) eventually resulting in conditional approval by the U.S. Food and Drug Administration in 2014. This drug is currently further developed in pediatric and Ph r/r, as well as in minimal residual disease-positive ALL, and might also offer clinical benefit for patients with non-Hodgkinʼs lymphoma, especially for those with aggressive forms like diffuse large B-cell lymphoma. Another BiTE antibody construct in hemato-oncology designated AMG 330 targets CD33 on acute myeloid leukemia blast cells. After showing promising ex vivo activity, this drug candidate has recently entered phase 1 clinical development, and has further indicated potential for combination with checkpoint inhibitors. In solid tumor indications, three BiTE antibody constructs have been tested in phase 1 studies so far: anti-EpCAM BiTE AMG 110, anti-CEA BiTE MEDI-565/AMG 211, and anti-PSMA BiTE BAY2010112/AMG 212. Pertinent questions comprise how to maximize BiTE penetration and T-cell infiltration of the tumor while simultaneously minimizing any adverse events, which is currently explored by a continuous intravenous infusion approach. Thus, BiTE antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need.