title: Bispecific antibodies engage T cells for antitumor immunotherapy.
abstract: BACKGROUND
  Although considerable evidence supports the hypothesis that T cells play a critical role in the immune response against cancer, the ability to mount and sustain tumor-specific cellular responses in vivo remains a challenge. A strategy that harnesses the cytotoxic advantage of T cell therapy is the use of bispecific antibodies designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex, but only in the presence of a tumor antigen. While antibody constructs with dual specificity were first described as anticancer therapeutics over 25 years ago, it was not until recently that one subclass of bispecific single-chain antibody, the bispecific T cell engager (BiTE), emerged as superior to previous iterations in achieving efficacy in animal models and early clinical trials.
  
  
  METHODS
  The evolution of bispecific antibodies in antitumor immunotherapy is reviewed and the greatest hurdles impeding their clinical translation are discussed, specifically in the context of immunoprivileged sites as is the case for intracerebral malignancy.
  
  
  CONCLUSIONS
  The BiTE platform has great potential in the treatment of malignant disease. Despite burgeoning interest in bispecific antibodies and permutations thereof, the issues of stability and cost-effective production persist as obstacles.
authors: Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, Division of Neurosurgery, Department of Surgery, Durham, North Carolina 27710 , USA. bryan.choi@duke.edu
authors: Bryan D
authors: BD
authors: Choi
authors: Mingqing
authors: M
authors: Cai
authors: Darell D
authors: DD
authors: Bigner
authors: Ankit I
authors: AI
authors: Mehta
authors: Chien-Tsun
authors: CT
authors: Kuan
authors: John H
authors: JH
authors: Sampson
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000266:history / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D019496:Cancer Vaccines / Q000266:history / Q000494:pharmacology*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects*
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D019496:Cancer Vaccines