Figure 6.

Improving the tumor penetration of ADCs in solid tumors through co-administration of matching non-conjugated (‘naked’) antibody therapy. (A) The administration of ADCs as a monotherapy may result in only perivascular distribution into the tumor due to rapid biding of target antigens just outside of the vasculature. (B,C) In theory, this binding site barrier can be overcome by providing ‘naked’ mAb therapy to compete for target antigen sites—resulting in ADCs to travel further into the tumor to find available antigen to bind. However, administration of the combination of ADC and naked mAb may also inhibit the clearance of the ADC by the IIS/MPS. Thus, the increased delivery of the ADC in combination with mAb may be due an overall higher systemic/serum exposure resulting in the potential for increased delivery into the tumor. The effects of co-administration of ADCs and mAb on saturation of clearance via the MPS needs to be evaluated for each combination regimen.