Follicular lymphomas (FL) account for 35-40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody rituximab (RTX). The development of type II anti-CD20 MAb obinutuzumab (GA101) aims to further improve treatment. Here we show using FL cells that RTX and GA101 displayed similar activity on RL cells cultured in 2D. As 2D culture cannot mimic tumor spatial organization, conventional 2D models may not reflect the effects of antibodies as they occur in vivo. Thus, we created a NHL 3D culture system, termed multicellular aggregates of lymphoma cells (MALC), and compared RTX and GA101 activity. Our results show that both antibodies display greater activity towards FL cells in 3D culture compared to 2D culture. Moreover, we observed that in the MALC model GA101 was more effective than RTX in inhibiting tumor growth through induction of (lysosomal) cell death and senescence; and in inhibiting intracellular signaling pathways such as mTOR, Akt, PLCgamma and Syk. Altogether, our study demonstrates that spatial organization strongly influences response to antibody treatment supporting the use of 3D models for the testing of therapeutic agents in NHL.
- Copyright © 2013 by The American Association of Immunologists, Inc.