According to Damon Hostin, marketing development manager, Strategic Diagnostics has optimized the procedure, overcoming problems such as poor immune response by the host animal that plagued the procedure in the past. “We broke the method up into its component parts, and then optimized the conditions of each step,” said Hostin. “The algorithms for protein modeling have improved greatly in the last few years, so we are able to generate DNA sequences for peptides that are much better immunogens.”
With present-day modeling, peptides can be produced that assume their appropriate 3-D folding, thereby ensuring that the authentic epitopes are available for stimulating the immune system of the host.
This means that antibodies can be produced on an assembly-line basis, avoiding the difficulty of expressing and purifying a protein that could be unstable and technically demanding. Over the course of its existence, the company has produced around 1,500 antibodies at its GMP facility, Hostin reported.
According to Leigh Anderson, Ph.D., CEO of the Plasma Proteome Institute, the search for cancer biomarkers is a harsh, unforgiving affair. “It is a high-risk enterprise, with a 99% attrition rate,” he says. “This may be a reflection of the huge level of genetic variability within the human population.”
What Works and What Doesn’t
There is no guiding theory of biomarker science, Dr. Anderson noted, and it is completely empirically based. There is also a plethora of candidates that are difficult to resolve, and verification is slow, and appears to be a rate-limiting step. Despite the critical importance of cancer biomarkers in early detection, the protein-based in vitro diagnostics industry is only 1% as large as the pharmaceutical business. This may explain why, after years of investigation, the number of clinically successful biomarkers obtained through proteomics is zero.
“The major roadblock is the need for large (one to two thousand patients) sample sets when one is evaluating a candidate biomarker,” Dr. Anderson said. “There are lots of possible biomarkers out there, but the amount of effort required for a really decisive assessment is immense.”
Karin A. Hughes, Ph.D., worldwide product director for sepsis, stroke and protein C at Biosite, feels the problem may lie in the fact that discovery tools do not intersect with validation tools. “There are a large number of potential biomarkers but discovery technologies are not suitable for biomarker validation. Because the skills to validate them do not always reside in-house nor with discovery partners, biomarkers get stuck in the research phase and are not moving forward.”
In order to move cancer treatment forward, an emphasis on diagnosis as opposed to therapy will be required. With therapeutic protocols running to hundreds of thousands of dollars per patient, effective biomarkers that detect cancer while it is still treatable look like a pretty good investment.
Dr. Anderson is optimistic that this day is dawning. “We have a project in place with the NCI to study 300 possible cancer biomarkers,” he stated. “This will provide definitive information on the first large cohort of candidates.”
K. John Morrow Jr., Ph.D., is president of Newport Biotech Consultants and contributing editor for GEN. Web: www.newportbiotech.com. E-mail: [email protected]