Figure 4.

 Diagram of the background and the new concept of drug delivery using tumor stroma as a ligand. (A) Low molecular weight anticancer agents (black) can be distributed throughout the entire body, resulting in serious side effects. (B) Cytotoxic immunoconjugates (blue) accumulate selectively in the tumor tissue. Successful (upper) and failed (lower) immunoconjugate therapy is shown. (C) The newly developed immunoconjugate (i.e. anti‐fibrin chimeric IgG–branched‐PEG‐(SN‐38)₃) extravasates selectively from leaky tumor vessels, binds specifically to the fibrin network around the tumor vessels to create a scaffold, and then allows the effective, sustained release of SN‐38, an anticancer agent with time‐dependent effects, from the scaffold. Because this released anticancer agent is of a low molecular weight, it is subsequently distributed throughout the entire tumor stroma, which normally acts as a barrier, and induces damage not only to tumor cells, but also to tumor vessels.