Fc engineering of a fully humanized anti-CD147 monoclonal antibody enhances ADCC against T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma.

T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) are aggressive hematologic malignancies with limited targeted treatment options and poor clinical outcomes across all age groups. CD147 is a multifunctional transmembrane glycoprotein that is highly expressed in various cancers, including T-cell leukemia and lymphoma. Its involvement in tumor progression and immune evasion makes CD147 a promising target for cancer immunotherapy. Monoclonal antibody-based immunotherapy can eliminate tumor cells not only by blocking oncogenic signaling pathways but also by engaging immune effector cells through antibody-dependent cellular cytotoxicity (ADCC). Enhancing ADCC has therefore emerged as a crucial strategy to enhance the therapeutic efficacy of anti-cancer antibodies. This study aimed to evaluate the functional activity of a fully humanized Fc-engineered anti-CD147 monoclonal antibody, HuM6-1B9-5M, which was designed to enhance ADCC by introducing five Fc mutations (L235V/F243L/R292P/Y300L/P396L). HuM6-1B9-5M was successfully expressed in HEK293T cells and retained CD147 binding activity and specificity comparable to those of the parental antibody. Biolayer interferometry against CD147 confirmed that Fc substitutions did not adversely affect antigen-binding affinity. Functional assays using PBMC effector cells demonstrated enhanced ADCC activity of HuM6-1B9-5M relative to the wild-type antibody (HuM6-1B9-WT) against Jurkat and SupT1 cell lines, representing T-ALL and T-LBL models, respectively.