The drug targets an enzyme called membrane type 1 matrix metalloproteinase (MT1-MMP), also known as MMP-14.
Conventional toxins used in cancer treatment are unable to distinguish tumor cells from healthy tissue, resulting in increased toxicity for the patient undergoing therapy. In contrast, BDC is composed of two parts: a toxin and a specific high-affinity molecule called Bicycle, which is designed to bind only to a specific structure found on tumor cells.
Besides its high target specificity delivers the toxin directly to tumor cells, Bicycle has other inherent properties — such as rapid penetration into the tumor, low systemic exposure, and rapid kidney clearance — believed to minimize the drug’s toxicity.
How BT1718 works
The MT1-MMP enzyme is found in abundance on the surface of many solid tumors, such as breast, lung, ovarian, and colon cancer. Its increased production has been linked to poor cancer prognoses due to MT1-MMP’s role in cell migration and cancer metastasis.
BT1718 uses MT1-MMP as the target structure for the delivery of the toxin. This means that the Bicycle component links to MT1-MMP found on cancer cells, and because of its low molecular weight and favorable volume of distribution, BT1718 has the potential to penetrate the tumor cell rapidly and “kill” it.
BT1718 is still in pre-clinical testing, but data show that the drug is highly efficient in eradicating tumors and preventing their return in mice that were grafted with tumors. Tumor cells express the MT1-MMP enzyme (which BT1718 targets) in excessive amounts, meaning there is more of the enzyme’s messenger molecule (or mRNA) and, hence, a potentially more efficient therapy.
Cancer Research UK, the largest charitable cancer organization in the U.K., will sponsor and fund a Phase 1 study testing BT1718. The trial is expected to start in 2017 and will be co-managed by Bicycle and Cancer Research UK.
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