title: Harnessing T cells to fight cancer with BiTE® antibody constructs--past developments and future directions.
abstract: 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-Hodgkin's 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.
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Matthias
authors: M
authors: Klinger
authors: Amgen Inc., Thousand Oaks, CA, USA.
authors: Jonathan
authors: J
authors: Benjamin
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Roman
authors: R
authors: Kischel
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Sabine
authors: S
authors: Stienen
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Gerhard
authors: G
authors: Zugmaier
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D015202:Protein Engineering; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C510808:blinatumomab
keywords: acute lymphoblastic leukemia; acute myeloid leukemia; bispecific T-cell engager (BiTE®); blinatumomab; immunotherapy; non-Hodgkin's lymphoma