Fcγ Receptor-Dependent Internalization and Off-Target Cytotoxicity of Antibody-Drug Conjugate Aggregates

• Published in: Pharmaceutical research Vol. 39; no. 1; pp. 89 - 103
• Main Authors: Aoyama, Michihiko, Tada, Minoru, Yokoo, Hidetomo, Demizu, Yosuke, Ishii-Watabe, Akiko
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2022; Springer Nature B.V
• Subjects: Antibodies; Antibodies, Monoclonal - pharmacology; Antineoplastic Agents, Immunological - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blocking antibodies; Cell activation; Cell Line; Cell Line, Tumor; Cytotoxicity; Humans; Hydrophobicity; Immunoconjugates - pharmacology; Internalization; Medical Law; Monoclonal antibodies; Pharmacology/Toxicology; Pharmacy; Receptors, IgG; Research Paper; Tumors; aggregation; off-target toxicity; Fcγ receptors; Antibody-drug conjugates

Purpose Antibody-drug conjugates (ADCs), which are monoclonal antibodies (mAbs) conjugated with highly toxic payloads, achieve high tumor killing efficacy due to the specific delivery of payloads in accordance with mAbs’ function. On the other hand, the conjugation of payloads often increases the hy...