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New Technology Generates Cancer Killing Antibody Drug Conjugates

By BiotechDaily International staff writers
Posted on 11 Mar 2014
Image: In order to overcome the known limitations inherent to chemical conjugation of small molecule toxic drugs to antibodies, NBE-Therapeutics has developed a patent-pending technology for the specific enzymatic conjugation of drugs to antibodies (Photo courtesy of NBE-Therapeutics).
Image: In order to overcome the known limitations inherent to chemical conjugation of small molecule toxic drugs to antibodies, NBE-Therapeutics has developed a patent-pending technology for the specific enzymatic conjugation of drugs to antibodies (Photo courtesy of NBE-Therapeutics).
A novel technology for generation of specific toxin-bearing antibodies for treatment of cancer has been validated in a recent series of proof-of-concept studies.

NBE-Therapeutics (Basel, Switzerland) presented evidence of the successful validation of its enzymatic SMAC-Technology for the generation of potent next-generation antibody drug conjugates (ADCs) at the international World ADC summit held in Frankfurt (Germany).

NBE-Therapeutics' patent-pending SMAC (sortase-mediated antibody conjugation)-Technology utilizes highly selective sortase enzymes for site-specific and efficient conjugation of toxic payloads to therapeutic antibodies. 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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