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Summary

A UK company has developed a unique drug screening system that starts from human cell lines (produced using a combination of proprietary methods). It simultaneously tests candidate compounds on both healthy cells and those with one or more tailored cancer mutations for toxicity and selectivity. The patented technology could slash years off the drug development cycle and add immediate market value to compounds that pass the screen. The company is seeking cancer drug development partners.

Full description

Many researchers agree that the future of cancer treatment lies in so-called targeted therapeutics. This approach aims to find drugs that target defective molecules or processes only present in cancer cells. Using gene knockdowns and knockouts, signal transduction knowledge, and more, todays researchers work toward treatment concoctions that fight cancer. No doubt good progress has been made and tools like gene over-expression and RNA silencing are quite common. But even these advanced tools have serious drawbacks when studying diseases like cancer since they fail to mimic the complex interactions present in diseased and healthy cells. At present drug candidates are screened using cancer models, without really knowing how they work, and how they impact healthy cells.

Now a UK company has developed a unique process that enables researchers to simultaneously study the effects of cancer drug candidates on both healthy and mutated cells. Most importantly it uses human cell lines (see below) and not a human or non-human cancer model. The new tool enables researchers to determine quickly whether candidate compounds target a specific cancer defect and whether they have a therapeutic window. It enables a whole step in the programme to be skipped and could slash years off the lengthy drug development process. A second business benefit is adding value. Candidate compounds that are shown to be non-toxic and selective are more likely to be successful in human clinical trials. Such compounds would immediately have a higher market value.

The screening tool is a collection of human cell lines that are produced using a combination of proprietary methods. These consist of controls and mutants in pathways associated with common cancers. The cell lines are either wild or have one or more mutations in predetermined positions (i.e., isogenic except for this mutation, see figure 1). The mutation production methods greatly surpass the efficiency of conventional methods. Both wild and mutant cells carry reporter genes with different fluorescence spectra. When these are co-cultured in arrays, they provide direct readouts of the respective growth rates in the presence of a candidate compound.

The screening tool has already been used to identify specific compounds out of a library of 29,000 that selectively inhibit cells carrying a mutated gene called Ras (see figure 2). Although the technology the company owns is a platform, and could be used in all sorts of drug screening programmes, the current focus is on cancer. The collection of cell lines consists of controls and mutants in pathways associated with common cancers.

The company is interested in licensing out cell lines, collaborating in screening programmes, and generating tailored cell lines.

Innovative Aspects

The companys cell collection is the first commercial source of identical human cell lines, differing simply in one or more positions in cancer-related genes.

The key advantages of using these cell lines include:
" Quick establishment of a direct correlation between a target (including gene variants) and the action of a drug.
" Quick validation of a therapeutic window for a drug. Drugs that have passed this screen are much more likely to pass the downstream development phases.
" High-throughput screening of multiple compounds versus multiple cell lines.
" Collectively, these advantages allow one to save a vast number of experiments in the pre-clinical phase, and give a high-quality estimate for the success of the downstream clinical phase.

Partner expertise sought:

- Type of partner:
Industry.

- Specific area:
Cancer drug developers.

- Collaboration sought:
Provision of cell lines, establishing screening programmes, generation of tailored cell lines. The type of deal and terms of exclusivity can vary.