Figure 2.

Therapeutic antibodies targeting TfR1 can disrupt iron uptake through multiple non-mutally exclusive mechanisms. Neutralizing antibodies inhibit Tf from binding to TfR1, blocking the uptake of iron. Non-neutralizing antibodies still allow the binding of Tf, but may disrupt TfR1 cycling and induce degradation of TfR1. Binding of multivalent antibodies, such as IgM, to TfR1 may result in extensive cross-linking of the receptor and inhibition of its internalization. All of these ultimately lead to iron deprivation that can either sensitize cells to other anti-cancer agents or can cause the inhibition of proliferation and induction of caspase activation resulting in apoptosis. This figure was adapted and reprinted with permission from Springer Nature: Humana Press, Inc., Daniels et al. Targeting the transferrin receptor to overcome resistance to anti-cancer agents. In Sensitization of Cancer Cells to Chemo/Immuno/RadioTherapy (91).