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Experimental Drug Kills Myeloma Cells in Lab, Trial Planned

Guido Franzoso

Guido Franzoso (Imperial College London)

13 October 2014. Medical researchers at Imperial College London in the U.K. developed an experimental drug that in lab and animal tests kills multiple myeloma cancer cells without the toxic side effects of other cancer drugs. The team led by Imperial medical professor Guido Franzoso published its findings today in the journal Cancer Cell, with a clinical trial of the new drug expected to begin by the end of next year. In addition, a spin-off company was formed to commercialize the research.

Multiple myeloma is a cancer of the plasma cells, white blood cells help fight infections by making antibodies that recognize invading germs. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal proteins that cause kidney problems. American Cancer Society expects some 24,000 cases of multiple myeloma to occur in the U.S. this year, causing more than 11,000 deaths.

The new drug tested by Franzoso and colleagues, code-named DTP3, addresses a property that enables cancer cells to keep multiplying well beyond normal lifetimes. A protein called nuclear factor kappa B, known to have a role in inflammation and immune systems, also contributes to cancer growth by extending the lifetimes of cancer cells. Developing therapies that address this protein, however, is difficult since it plays a role in supporting both healthy and cancerous cells, and directly targeting the protein can lead to toxic side effects.

The Imperial team — with colleagues elsewhere in the U.K., Europe, and the U.S. — looked for a target in the process between nuclear factor kappa B and cancer cells, which would interrupt signals feeding cancer cells, but not healthy cells. The researchers discovered a set of interacting proteins identified as GADD45-beta and MKK7 that keeps cancer cells alive. The team then screened some 20,000 molecules for activity against these proteins that led to two molecules that disrupt GADD45-beta/MKK7, and after refinements, the peptide-based candidate DTP3.

In their lab tests, researchers found DTP3 disrupts GADD45-beta/MKK7 proteins and kills multiple myeloma cells about as effectively as the current cancer drug bortezomib, marketed as Velcade by Millennium Pharmaceuticals. The tests showed as well DTP3 is 100 times better able to target cancer rather than healthy cells, thus with far less toxicity. In addition, the team found DTP3 kills multiple myeloma cancer cells grafted in lab mice, with no apparent side effects.

The researchers plan to take DTP3 into an early-stage clinical trial and received £3.9 million ($6.3 million) from the Medical Research Council, a science funding agency in the U.K., to fund the work through next year.  A spin-off company, Kesios Therapeutics Ltd., has been formed as well to commercialize the research on DTP3. The company received last week equity seed financing of £1.85 million ($3 million) from Imperial’s technology transfer fund to establish the business and begin operations.

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