Emerging anti-tumour therapy
Linkage of a tumour-specific peptide with an established anticancer agent, paclitaxel, may be the basis for a targeted highly specific anti-tumour therapy, according to research by scientists from NaPro BioTherapeutics and the University of Alabama.
Linkage of a tumour-specific peptide with an established anticancer agent, paclitaxel, may be the basis for a targeted highly specific anti-tumour therapy, according to research by scientists from NaPro BioTherapeutics and the University of Alabama.
The selective tumour-specific conjugate appears to target a wide variety of cancers expressing the specific peptide receptor.
'This emerging platform combines the science and known cytotoxic properties of taxanes, compounds with which NaPro has considerable experience, with a proprietary peptide linkage/receptor specific strategy,' said Leonard Shaykin, chairman and ceo of NaPro. 'We intend to begin clinical trials with at least one such compound in 2004.'
NaPro researchers are targeting the bombesin receptor, common to a wide variety of tumour types. In vitro experiments have determined that a specific paclitaxel-bombesin peptide ligand (NBT-300) conjugate is able to deliver cytotoxic concentrations of taxanes via the bombesin receptor into several specific cancer cell lines, including breast, small cell lung, non-small cell lung, head and neck squamous cell, pancreatic, prostate, and neuroblastoma.
'Our early studies demonstrate that, upon binding to its receptor, our proprietary conjugate is specifically transported into these cancer cell lines, cleaved, and the intracellularly released paclitaxel destroys the tumour. Levels of cytotoxicity varied with the level of bombesin receptor expression in each tumour line and the paclitaxel concentration. The preliminary data are strongly supportive of a peptide receptor-mediated approach for the treatment of bombesin receptor expressing cancers. Potential advantages may include a lower side effect profile for our conjugate compound and a higher level of tumour 'kill' than an equivalent non-conjugated cytotoxic,' commented Dr Lawrence Helson, vice president, Bioresearch at NaPro. 'We may also be able to deliver a therapeutic dose to tumours by means of these conjugates which heretofore, because of systemic toxicity, was not possible.'