Figure 6.

Proposed apoptotic pathways triggered by GD2-specific mAb 3F8. Following the internalization of both mAb 3F8 and GD2 into endosomes, the increase of GD2 containing endosomes triggers both extrinsic and intrinsic caspase-dependent and caspase-independent apoptotic pathways. They include the activation of caspase 3, 7, and 8, the release of cyt c and AIF, and the downregulation of both survivin and Apaf-1 without the activation of caspase 9. Apaf-1 downregulation is believed to be responsible for the lack of detectable caspase 9 activation. Survivin downregulation is believed to increase the sensitivity of cells to both caspase-dependent and caspase-independent apoptosis. Solid lines indicate the direct effects while dash lines indicate effects with either unknown or indirect mechanisms.