Cytotoxic antibody-drug conjugates targeting the tumor-associated antigen PRAME
Antibody-drug conjugates (ADCs) are a promising therapy for cancer. A team of researchers from the Laboratory of Molecular Design and Synthesis together with colleagues from the Laboratory of Molecular Diagnostics and the Laboratory of Lipid Chemistry of the IBCh RAS, as well as the N.N. Blokhin Russian Cancer Research Center, developed several approaches to the synthesis of conjugates of antibodies to the tumor-associated antigen PRAME with the anticancer drugs doxorubicin and MMAE. The team performed site-specific conjugation by periodate oxidation of glycans followed by bioorthogonal reactions: oxime ligation and CuAAC. Cyanine dyes were introduced into the structure of the linkers for easy determination of the stoichiometry of the conjugates. As a result, the possibility of creating antibody-drug conjugates targeting the PRAME antigen was shown for the first time. The work was published in the International Journal of Molecular Sciences.
april 3, 2023