An integrated approach to identify normal tissue expression of targets for antibody‐drug conjugates: case study of TENB2

• DOI: 10.1111/j.1476-5381.2012.02138.x
• Publication Date: 2012-08-13T12:03:25Z
• Authors: C Andrew Boswell; Eduardo E Mundo; Ron Firestein; Crystal Zhang; Weiguang Mao; Herman Gill; Cynthia Young; Nina Ljumanovic; Shannon Stainton; Sheila Ulufatu; Aimee Fourie; Katherine R Kozak; Reina Fuji; Paul Polakis; Leslie A Khawli; Kedan Lin
• Keywords: Antibody-drug conjugate; Conjugate

The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by differential expression between normal and pathological tissues. ability to identify visualize target in tissues could reveal causes for target-mediated clearance observed pharmacokinetic characterization. TENB2 is a prostate cancer associated with progression poorly differentiated androgen-independent tumour types, ADCs specific are candidate therapeutics. objective this study was locate antigen tissues, thereby elucidating underlying clearance.A series pharmacokinetics, tissue distribution mass balance studies were conducted mice using radiolabelled anti-TENB2 ADC. These data complemented non-invasive single photon emission computed tomography - X-ray imaging immunohistochemistry.The intestines identified as saturable sink that contributes, at least part, rapid antibody its drug conjugate rodents. As proof concept, we also demonstrated selective disposition ADC tumoural environment vivo LuCaP 77 transplant mouse model. High uptake despite presence sink, specificity confirmed blockade.Our findings provide anatomical location biological interpretation antibodies corresponding conjugates. Further investigations may be beneficial addressing relative contributions from both