ABSTRACT
BACKGROUND/AIM: Adult T-cell leukemia (ATL) is a hematological malignancy caused by infection with human T-cell leukemia virus type 1 (HTLV-1). Chemotherapy, antibody therapy, and bone marrow transplantation are used to treat this disease, however, median survival time has not been significantly improved. Our aim was to develop and evaluate a novel antibody-drug conjugate (ADC) with regards to cell cytotoxicity and target specificity. MATERIALS AND METHODS: In this study, we have constructed a novel ADC, which is composed of an anti-CD70 single chain Fv-Fc antibody conjugated with the anticancer agent emtansine using a novel antibody modification method. Cell cytotoxicity and target specificity were assessed using a cell proliferation assay. RESULTS: The anti-CD70 ADC selectively killed HTLV-1-infected cells and ATL cells without affecting other cells. CONCLUSION: The anti-CD70 ADC offers some chemotherapeutic potential for the treatment of ATL.
Subject(s)
CD27 Ligand/antagonists & inhibitors , Immunoconjugates/pharmacology , Leukemia-Lymphoma, Adult T-Cell/immunology , Maytansine/pharmacology , Single-Chain Antibodies/pharmacology , Adult , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Humans , Jurkat Cells , Leukemia-Lymphoma, Adult T-Cell/therapy , Male , Middle AgedABSTRACT
Artificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. CCAP was applied for the preparation of an antibody-drug conjugate and a bispecific antibody to demonstrate the usefulness of this method.
