Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy
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REVIEW – CANCER RESEARCH
Bispecific antibodies targeting dual tumor‑associated antigens in cancer therapy Shuyu Huang1,2 · Sander M. J. van Duijnhoven1 · Alice J. A. M. Sijts2 · Andrea van Elsas1 Received: 12 August 2020 / Accepted: 21 September 2020 © The Author(s) 2020
Abstract Purpose Bispecific antibodies (BsAbs) have emerged as a leading drug class for cancer therapy and are becoming increasingly of interest for therapeutic applications. As of April 2020, over 123 BsAbs are under clinical evaluation for use in oncology (including the two marketed BsAbs Blinatumomab and Catumaxomab). The majority (82 of 123) of BsAbs under clinical evaluation can be categorized as bispecific immune cell engager whereas a second less well-discussed subclass of BsAbs targets two tumor-associated antigens (TAAs). In this review, we summarize the clinical development of dual TAAs targeting BsAbs and provide an overview of critical considerations when designing dual TAA targeting BsAbs. Methods Herein the relevant literature and clinical trials published in English until April 1st 2020 were searched using PubMed and ClinicalTrials.gov database. BsAbs were considered to be active in clinic if their clinical trials were not terminated, withdrawn or completed before 2018 without reporting results. Data missed by searching ClinicalTrials.gov was manually curated. Results Dual TAAs targeting BsAbs offer several advantages including increased tumor selectivity, potential to concurrently modulate two functional pathways in the tumor cell and may yield improved payload delivery. Conclusions Dual TAAs targeting BsAbs represent a valuable class of biologics and early stage clinical studies have demonstrated promising anti-tumor efficacy in both hematologic malignancies and solid tumors. Keywords Bispecific antibodies · Dual targeting · Cancer therapy · Clinical trials · Literature review Abbreviations ADC Antibody drug conjugate ADCC Antibody-dependent cell-mediated cytotoxicity ADCP Antibody-dependent cellular phagocytosis ALL Acute lymphoblastic leukemia BICEs Bispecific immune cell engagers BsAb Bispecific antibody BTD Breakthrough therapy designation CDC Complement-dependent cytotoxicity CMC Chemistry: manufacturing: and controls DR5 Death receptor 5 DVD-Ig Dual-variable-domain immunoglobulin EGFR Epidermal growth factor receptor EMA European Medicines Agency * Andrea van Elsas [email protected] 1
Aduro Biotech Europe, Oss, The Netherlands
Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands
2
EpCAM Epithelial cell adhesion molecule Fab Antigen binding fragment FAP Fibroblast activation protein Fc Fragment crystallizable FcRn Neonatal Fc receptor FDA Food and Drug Administration HCL Hairy cell leukemia HGF Hepatocyte Growth Factor IgG Immunoglobulin G LAMP3 Lysosome-associated membrane glycoprotein 3 mAbs Monoclonal antibodies MET Mesenchymal-epithelial transition factor MOA Mechanism of action NRG1 Neuroregulin1
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