Figure 3.

Multivalent antibody presentation on the surface of nanoparticles facilitates receptor activation. Insufficient agonism of target receptors represents a common mode of resistance to many therapies, as observed with antibodies directed against DR5, for example. (A) When applied in free format, antibodies show limited ability to induce oligomerisation and cross-linking of DR5 to the extent required for downstream signal transduction. (B) However, the concentrated display of antibodies on a nanoparticle surface allows for multivalent engagement of DR5 beyond the threshold needed for receptor activation. Signalling is initiated in response, involving recruitment of FADD and activation of initiator and executioner caspases that mediate apoptotic cell death.