Obinutuzumab (GA101) Displays Higher Efficiency Than Rituximab in a Follicular Lymphoma 3D Model

Abstract 4868

Follicular lymphomas (FL) account for 35–40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody (MAb) rituximab (RTX). The development of type II anti-CD20 MAb obinutuzumab (GA101) aims to improve treatment further. Using FL cells, here we showed that RTX and GA101 displayed similar efficiency towards 2D culture. However, 2D culture does not mimic tumor spatial organization and conventional 2D models do not reflect the effects of MAbs seen from preclinical and in vivo studies. Thus, we created a NHL 3D culture system, the so-called multicellular aggregates of lymphoma cells (MALC), and compared RTX with GA101 activity. Our result showed that both MAbs displayed greater bioactivity towards FL cells in 3D culture compared to 2D culture. Moreover, we observed that GA101 was more effective than RTX in inhibiting tumor growth through induction of apoptosis, lysosomal cell death and senescence. GA101 was also more effective than RTX in inhibiting intracellular signaling pathways such as mTOR, Akt, PLCgamma and Syk. Altogether, our study demonstrates that spatial organization strongly influences response to MAbs treatment. Additionally, we provide evidences that GA101 is more effective than RTX in inhibiting FL development in MALC model, which suggests the possibility for better patient treatment with GA101.