Antibody-Drug Conjugates
Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to potent cell-killing drugs. By employing a rapidly internalizing antibody, one is able to deliver the drug inside target cells. The environment inside the cell cleaves the linker, which releases the cytotoxic drug and allows it to have the desired effect. Until released, the drug is inactive, thereby sparing non-target cells many of the toxic effects of traditional chemotherapy.
The key components of Seattle Genetics' proprietary ADC technology are the stable, enzyme cleavable linkers and the highly potent, synthetic cytotoxic drugs. The linker holds and then releases the drug from the antibody once inside of target cells. Seattle Genetics' ADC technology utilizes novel linkers that have been shown in preclinical models to be much more stable in blood than conventional means of attaching drugs to antibodies.
The company has also developed cytotoxic drugs, such as Auristatin derivatives, that have highly potent activity against tumor cells in preclinical models. Importantly, since both the linker and drug components are synthetic, Seattle Genetics' ADC technology is readily scalable, representing an improvement over natural product drug systems that are often more difficult to produce.
ADC Product Candidates
SGN-35, SGN-75 and anti-CD19 ADC are comprised of a potent Auristatin derivative and a novel linker system that is stable in blood yet releases its drug payload inside of target cells via enzymatic cleavage. SGN-35 is in phase I clinical trials for Hodgkin lymphoma and other CD30-positive hematologic malignancies. SGN-75 and anti-CD19 ADC are in preclinical development.
Seattle Genetics also has multiple other ADCs for both carcinomas and hematologic malignancies that are being studied in preclinical model systems.
ADC Collaborations
Seattle Genetics has license agreements with Genentech, CuraGen, Bayer, Progenics, Daiichi Sankyo and MedImmune, a wholly-owned subsidiary of AstraZeneca, to provide them with access to our ADC technology. These collaborations all involve payments by our corporate partners of license fees, milestones and royalties on net sales of products incorporating our ADC technology. Our corporate partners are responsible for development, manufacturing and commercialization of any ADC product candidates that result from the collaborations.
We also have a co-development agreement with Agensys, a wholly-owned subsidiary of Astellas Pharma, to jointly develop up to two ADC products. Under the agreement, Agensys will provide proprietary targets and monoclonal antibodies to be utilized with Seattle Genetics' proprietary ADC technology. The companies will share research and development costs on up to two ADC programs, and share equally in any profits.
For more information about ADC technology collaboration opportunities, please email businessdevelopment@seagen.com.
ADC Publications
Selected publications related to Seattle Genetics' ADC technology are listed below. Click here to view additional publications and abstracts on Seattle Genetics' technologies and product candidates.
Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a
potential therapeutic target for anti-CD70 antibody-drug conjugates
Cancer Research 2006
Enhanced activity of monomethylauristatin F through monoclonal antibody
delivery: effects of linker technology on efficacy and toxicity
Bioconjugate Chemistry 2006
Lysosomal trafficking and cysteine protease metabolism confer target-specific
cytotoxicity by peptide-linked anti-CD30-auristatin conjugates
Journal of Biological Chemistry 2006
Arming antibodies: prospects and challenges for immunoconjugates
Nature Biotechnology 2005
In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin
immunoconjugate
Clinical Cancer Research 2005
Efficient
Elimination of B-Lineage Lymphomas by Anti-CD20-Auristatin Conjugates
Clinical Cancer Research 2004
Effects of drug loading on the antitumor activity of a monoclonal
antibody-drug conjugate
Clinical Cancer Research 2004
Secondary
mAb-vcMMAE conjugates are highly sensitive reporters of antibody internalization
via the lysosome pathway
Bioconjugate Chemistry 2004
Development
of potent monoclonal antibody auristatin conjugates for cancer therapy
Nature Biotechnology 2003