CD44 and neoplasm: The implementation of these approaches requires several critical features, such as (1) implementation of a tumor cell-selective binding module, (2) conditional accessibility of the heparan sulfate proteoglycan to prevent non-specific HSPG-dependent internalization, and (3) release of the antibody or the cargo from any membrane-bound target molecules in the endosome to allow endosomal escape and release into the cytosol (Figure 1C).