Seattle Genetics' next-gen antibody-drug conjugate tackles leukemia in the lab

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Seattle Genetics ($SGEN) has a flurry of presentations of clinical data at the 54th American Society of Hematology (ASH) annual meeting this year, and tucked within these is preclinical data on SGN-CD33A, one of its early-stage next-generation antibody-drug conjugates. Though the results are just in cell lines and mice so far, they give a hint of a hope for a treatment for drug-resistant acute myeloid leukemia (AML), a blood cancer with poor outcomes.

SGN-CD33A uses Seattle Genetics' next-generation technology and is made up of an antibody that targets the myeloid differentiation antigen CD33 (expressed on the surface of most AML cells), hooked up to pyrrolobenzodiazepine (PBD) dimer, a highly potent cancer drug.

In AML cells on the bench, at low doses, SGN-CD33A was quickly pulled inside the cells and damaged the DNA, leading to cell death. It was effective even in cells resistant to a number of other anti-leukemic agents. In mice models of AML, SGN-CD33A delayed tumor growth and improved survival. The company is planning a Phase I clinical trial for next year.

Because they are so specifically targeted, antibody-drug conjugates have potential to increase the efficacy of cancer treatment and reduce its side effects. Even though the first marketed antibody-drug conjugate, Mylotarg, was pulled by its developer Pfizer ($PFE) in 2010 for lack of efficacy, research into antibody-drug conjugates is a growing field. Roche's ($RHHBY) T-DM1 looks close to the market, as it is up for priority review with the FDA, with a decision due by late February. According to Seattle Genetics, there are about 30 antibody-drug conjugates in development, and more than half of these use its technologies.

- read the press release
- see the abstract

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