Enhanced Anti-CD37 Therapy for B-Cell Malignancies: The NNV024 Monoclonal Antibody Approach

A significant clinical demand exists for new treatment options for B-cell non-Hodgkin lymphomas (B-NHL) patients who are unresponsive to anti-CD20 therapies or have malignancies lacking CD20 expression. The CD37 antigen is highly expressed on malignant B-cells, making it an appealing target for therapy. A humanized anti-CD37 monoclonal antibody, NNV024, was developed with enhanced antibody-dependent cellular cytotoxicity (ADCC) through a process involving computational CDR-grafting, structure-based mutation, and selection based on low immunogenicity. The antibody was modified to be afucosylated to improve its ADCC effect.

In vitro and in vivo characterization of NNV024 confirmed its binding to human Fc gamma receptors, FcRn, and C1q. Its efficacy was evaluated using cell lines from various B-NHL subtypes and patient-derived B-CLL cells, demonstrating potent ADCC and antibody-dependent cellular phagocytosis (ADCP). NNV024 showed superior plasma pharmacokinetics and extended plasma half-life in transgenic mice. A comparative therapy study in a disseminated tumor model indicated that NNV024 provided a survival benefit over obinutuzumab.

The results indicate that NNV024 could be a promising therapeutic monoclonal antibody for treating B-cell malignancies and related autoimmune disorders.