click to enlarge Misregulation of protein metabolism can lead to unchecked proliferation and tumorigenesis. Millipore’s new anti-ubiquitin (Lys48-specific) monoclonal antibody allows researchers to visualize protein synthesis and degradation. The ubiquitin signal (red, left panel) is strongest in the nucleus (blue, right panel). (Source: Millipore)

In cancer research, antibodies provide an ever-expanding collection of tools that can be used in various ways, such as characterizing a drug target. Given the breadth of antibodies, some companies focus on specific types. “We hone in on several key areas,” says Terri Borree, product manager in the protein research group at Millipore in Temecula, Calif. At Millipore, those areas include signaling, cell migration, and cell death.

In signaling, for example, Millipore recently launched several key antibodies that target ubiquitin. As its name suggests, this protein gets expressed ubiquitously, at least in eukaryotes. It consists of 76 residues, and Millipore makes antibodies that target residues 48 and 63. “These are very specific targets,” say Borree. Millipore also makes antibodies and assays that target phosphatidylinositol 3 kinase (PI3K). “The majority of cancer pathways drive through this kinase,” says Borree, “so inhibition or activation of it is a key focus for many researchers.”

For cell migration, Rho-kinase activity is an example of a Millipore antibody target. “If you can inhibit that kinase’s activity,” says Borree, “then you could prevent the metastasis of cancer to other areas.”

In cell death, Millipore is looking carefully at autophagy, a lysosomal degradation process by which a cell degrades its own components, ultimately killing itself. “If we could promote autophagy in cancerous cells or damaged areas, the cells would start to digest themselves,” Borree explains. “If it could be triggered therapeutically, maybe we could cut off a cancerous pathway.”

Borree expects cancer research to focus on increasingly fine-tuned targets. “Researchers today are focused on very specific protein activities related to cancer rather than general pathways,” she says. “As academic researchers identify these new protein targets, our aim is to develop viable antibody solutions that researchers can use for validation purposes and possibly screening for therapeutics in drug discovery markets.”

New Pathways to Pursue

click to enlarge The AlphaLISA is a bead-based technology that can detect analytes in the femtomolar range. (Source: PerkinElmer)

Today’s pharmaceutical industry follows many new pathways. “It is moving more and more away from chemical entities to biopharmaceuticals,” says Martina Bielefeld-Sevigny, PhD, vice president and general manager research reagent solutions at PerkinElmer in Waltham, Mass. Many of these biologics are antibodies. An antibody can be directed against a surface receptor of a disease-related cell to make it easier for the immune system to detect and remove. In addition, antibodies can target receptors for growth factors. For example, cetuximab inhibits epidermal growth factor receptor (EGFR), preventing many steps in the malignant phenotype of cells expressing EGFR. Bielefeld-Sevigny adds, “When you have an antibody that can differentiate the surface of cancerous cells from healthy cells, you can target the antibody at the cancer marker and attach a radionuclide like ⁹⁰Yttrium or ¹¹¹Indium to the antibody. Then, when the antibody binds with the cell, the cell is damaged through irradiation. You get the most specifically targeted form of radiotherapy.”

Bielefeld-Sevigny and her colleagues at PerkinElmer help researchers find and analyze therapeutic antibodies by providing tools like AlphaLISA, which provides femtomolar sensitivity. AlphaLISA is a homogenous mix-and-read technology, which does not require any wash steps and can easily be automated. “When developing a new therapeutic antibody, a company might look through hundreds of thousands of clones to find the ones with the best characteristics and expression levels,” says Bielefeld-Sevigny.

About the Author
Mike May is a publishing consultant for science and technology based in Houston, Texas.