BI-1206: Overcoming Dual Resistance in Mantle Cell Lymphoma through Targeting FcγRIIb

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma (NHL) that often develops resistance to standard treatments such as CD20 antibodies, BTK inhibitors, and BCL-2 inhibitors. This resistance can lead to poor outcomes for patients. Recent research has indicated that Fc gamma receptors (FcγRs), particularly the inhibitory FcγR FcgRIIB (CD32B), are crucial in the efficacy of therapies. FcgRIIB can hinder the effectiveness of antibodies like rituximab by promoting its internalization and removal from the tumor cell surface, thereby reducing the activation of immune effector cells.

In this study, the expression of FcgRIIB was investigated in MCL cell lines and patient samples, revealing high levels of the receptor in all cases. The in vivo efficacy of BI-1206, a monoclonal antibody targeting FcgRIIB, was assessed using a patient-derived xenograft (PDX) model of MCL that exhibited resistance to both ibrutinib and venetoclax. The model demonstrated that BI-1206, when used alone or in combination with rituximab and lenalidomide, significantly reduced tumor growth in various organs.

The findings suggest that FcgRIIB is a promising target for MCL therapies, and BI-1206 shows potential in overcoming resistance to existing treatments. Further experiments are being conducted to explore the role of BI-1206 in enhancing rituximab-based therapies and overcoming resistance.

Disclosures include various consultancy roles and research funding from multiple pharmaceutical companies for one of the authors.