Figure 2.

Summary of factors influencing the delivery of therapeutic antibodies in solid tumors. 1) A multitude of factors, including antibody large size and affinity, antigen diversity, and altered permeability of vasculature, leading to the heterogeneous distribution of systematically administered antibodies in tumor tissues. 2) Hypoxia and pH dysregulation in the tumor microenvironment (TME) due to hypoperfusion, elevated interstitial fluid pressure (IFP) by aberrant vasculature, and dense extracellular matrix (ECM) influence the transport of therapeutic antibodies to intratumoral sites. 3) The clearance of antibodies occurs from both inside and outside the tumor. Systemic clearance of antibodies from plasma hampers the concentration gradient required for antibody diffusion into the tumor. In lower antibody doses concerning a total amount of target antigen, antigen-antibody complexes undergo endocytic consumption and degradation (also called target mediated drug disposition effect). Local endocytic clearance through antibody internalization decreases antibody penetration to the tumor site.