The collagen receptor

uPARAP

uPARAP is a collagen receptor which plays an important physiological role in collagen homeostasis by active internalization of collagen fragments. uPARAP displays highly efficient and constitutively active internalization and recycling properties

1

Extracellular collagen fibers are cleaved into smaller fragments by select matrix metalloproteases (MMPs)

2

Collagen fragments bind to endocytic receptor uPARAP on the cell surface

3

Collagen bound by uPARAP is actively endocytosed via clathrin-coated pits

4

uPARAP, and any bound collagen, is routed to early endosomes

5

uPARAP receptor is recycled to the cell surface for an additional internalization cycle

6

Collagen is further routed to lysosomes where is it broken down by proteases such as cathepsins

uPARAP displays a differentiated expression profile between healthy and cancer tissue, with several cancer types significantly overexpressing the receptor, including soft-tissue sarcoma, osteosarcoma, mesothelioma and glioblastoma multiforme (GBM).  

Additionally, uPARAP is found to be upregulated by cells in the stromal compartment in multiple indications, including breast-, colon-, pancreas- and prostate cancers. uPARAP is a recycling endocytic receptor with extremely rapid internalization kinetics, providing highly efficient entry for ADCs targeting uPARAP-expressing cells

uPARAP

Expression on tumor cells

  • Soft tissue sarcoma
  • Osteosarcoma
  • Mesothelioma
  • Glioblastoma

Total copy number in tumor cells

10,000 – 100,000

Expression on healthy tissue

Limited uPARAP expression in healthy tissues and in activated fibroblasts/myfibroblasts of surrounding stroma in certain tissues

High Internalization rate

Target and bound ligand internalization
within 5-10 minutes

Receptor recycling upon ligand binding and internalization

Yes

Adcendo has generated in-vivo proof of concept data with our lead uPARAP ADC asset in multiple target indications and with multiple payload MoAs.