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Harnessing T cells to fight cancer with BiTE ® antibody constructs – past developments and future directions
Author(s) -
Klinger Matthias,
Benjamin Jonathan,
Kischel Roman,
Stienen Sabine,
Zugmaier Gerhard
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12393
Subject(s) - blinatumomab , cancer research , lymphoma , antibody , medicine , immunotherapy , t cell , cancer , cytotoxic t cell , immunology , biology , immune system , cd19 , in vitro , biochemistry
Summary Bispecific T‐cell engager (Bi TE ® ) 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‐ CD 19 Bi TE ® 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‐Hodgkin's lymphoma, especially for those with aggressive forms like diffuse large B‐cell lymphoma. Another Bi TE ® antibody construct in hemato‐oncology designated AMG 330 targets CD 33 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 Bi TE ® antibody constructs have been tested in phase 1 studies so far: anti‐Ep CAM Bi TE ® AMG 110, anti‐ CEA Bi TE ® MEDI ‐565/ AMG 211, and anti‐ PSMA Bi TE ® BAY 2010112/ AMG 212. Pertinent questions comprise how to maximize Bi TE ® 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, Bi TE ® antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need.