Diagnostic and therapeutic potential a novel EpCAM-targeting antibody

What is it about?

In this work we present the characterization and therapeutic potential of 3-17I, a novel human EpCAM-targeting monoclonal antibody. This antibody was shown to specifically target EpCAM-positive cell lines. In addition, strong reaction was found in all lung, colon, and breast human tumor biopsies. The antibody was also found to be internalized into EpCAM-positive cancer cells where it accumulated in endosomes and lysosomes. The ribosomal-inactivating toxin saporin was linked to 3-17I, creating the per se non-toxic immunotoxin 3-17I-saporin, a promising candidate for the drug delivery technology photochemical internalization (PCI). PCI is based on a light-controlled destruction of endolysosomal membranes and subsequent cytosolic release of the sequestered payload upon light exposure. EpCAM-positive human cancer cell lines MCF7 (breast), BxPC-3 (pancreas), WiDr (colon), and the EpCAM-negative COLO320DM (colon), were treated with 3-17I-saporin in combination with the clinically relevant photosensitizer TPCS2a (fimaporfin), followed by exposure to light. No cytotoxicity was observed after treatment with 3-17I-saporin without light exposure. However, cell viability, proliferation and colony-forming capacity was strongly reduced in a light-dependent manner after PCI of 3-17I in the EpCAM positive cell lines.

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Why is it important?

EpCAM is found expressed on the majority of solid cancers (carcinomas) and is hence an attractive target for both cancer therapy and diagnosis.

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