In order for an ADC to effectively kill a cancer cell, it is not enough for the ADC to bind a target receptor expressed at the cell surface.
The ADC must be internalized, as well as processed correctly in intracellular compartments, in order to release and thereby activate the cytotoxic payload, which will otherwise remain inactivated, or result in degradation products benign to the cancer cell.
To this end, the properties of the ADC target receptor are key to selective and efficient drug delivery.
Where many clinical stage ADCs target receptors that are expressed in high copy-numbers, but rely on mainly more passive internalization methods, ADCendo has a unique focus on professional endocytic receptors with a strong and selective expression in particular types of cancer.
One such receptor, a collagen receptor named uPARAP, has been found to be expressed especially by cancer cells of soft-tissue sarcoma, as well as other cancer types, with a more limited expression in healthy tissue. uPARAP is a constitutively active, recycling endocytic receptor, that efficiently delivers bound cargo into the endosomal/lysosomal pathways, to efficiently mediate ADC processing and intracellular drug release in cancer cells.
We believe that by exploiting these mechanisms in our ADC design, we may potentially obtain more efficient ADC internalization, processing, and drug release, compared to more conventional targeting strategies.
Read more about these concepts in our list of relevant publications.