New Technology Generates Cancer Killing Antibody Drug Conjugates

Sortases are a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (leucine-proline-any amino acid-threonine-glycine), then a highly hydrophobic transmembrane sequence, then a cluster of basic residues such as arginine. Cleavage occurs between the threonine and glycine. Sortases occur in almost all gram-positive bacteria and the occasional gram-negative.

ADCs represent a new type of targeted therapy, in which highly potent cellular toxins (toxic payloads) are conjugated to cancer-specific antibodies allowing the targeted destruction of cancer cells without affecting healthy cells or tissue.

In proof-of-concept studies, it was demonstrated that SMAC-generated ADCs displayed the same potencies in cancer cell killing experiments as commercially available benchmark ADCs composed of identical antibody and toxin, even when significantly smaller amount of toxic payload was conjugated.

The company is now planning to leverage its SMAC-Technology for the development of a preclinical and clinical pipeline of next-generation ADC products, aimed at providing improved targeted therapies for difficult to treat cancers.

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