title: Immunogenicity assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine.
abstract: BACKGROUND
  Antibody-drug conjugates (ADCs) such as Kadcyla™ (ado-trastuzumab emtansine [T-DM1]) present covalently bound cytotoxic drugs, which may influence their immunogenicity potential compared with antibody therapies. Therefore, ADCs require assay strategies that allow measurement of responses to all the molecular components.
  
  
  RESULTS
  The immunogenicity strategy for T-DM1 used a risk-based, tiered approach that included screening and titration to detect antitherapeutic antibodies; confirmation of positive responses; and characterization to assess whether the immune response is primarily to the antibody or to the linker-drug and/or new epitopes in trastuzumab resulting from conjugation.
  
  
  CONCLUSIONS
  The tiered immunogenicity assay strategy for T-DM1 allowed detection of antitherapeutic antibodies to all components of the ADC in multiple nonclinical and clinical studies. Characterization strategies implemented in clinical studies provided additional insights into the specificity of the immune response.
authors: Department of Bioanalytical Sciences, Genentech, South San Francisco, CA 94080, USA.
authors: Montserrat
authors: M
authors: Carrasco-Triguero
authors: Joo-Hee
authors: JH
authors: Yi
authors: Randall
authors: R
authors: Dere
authors: Zhihua Julia
authors: ZJ
authors: Qiu
authors: Corinna
authors: C
authors: Lei
authors: Yanhong
authors: Y
authors: Li
authors: Connie
authors: C
authors: Mahood
authors: Bei
authors: B
authors: Wang
authors: Douglas
authors: D
authors: Leipold
authors: Kirsten Achilles
authors: KA
authors: Poon
authors: Surinder
authors: S
authors: Kaur
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D055261:Immunogenetic Phenomena; D008252:Macaca fascicularis; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine