Radiation therapy with tositumomab (B1) anti-CD20 monoclonal antibody initiates extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent cell death that overcomes resistance to apoptosis.

Purpose: The use of targeted radiation therapy (RT) in conjunction with anti-CD20 monoclonal antibodies (mAb) delivers high clinical response rates in B-cell lymphomas as part of radioimmunotherapy. The mechanisms underlying these impressive responses, particularly in patients whose lymphomas have become refractory to chemotherapy, are poorly understood.

Experimental Design: In this study, we have investigated the signaling pathways and mode of cell death induced in B-cell lymphoma cells after the combination of RT and either type I (rituximab) or type II (tositumomab/B1) anti-CD20 mAb.