By Monica Heger
This article was originally published April 11.
Under a newly funded project, researchers at the Fred Hutchinson Cancer Research Center and Hutch spinout Adaptive TCR will sequence the T-cells and B-cells of 100 volunteers, searching for marks of exposure to 17 different pathogens.
The three-year, proof-of-principle project is funded through a $1 million grant from the Keck Foundation. If successful, it could be a step toward the use of sequencing as a replacement for current titering methods to diagnose infection.
Adaptive TCR will conduct the sequencing at its Seattle facilities and will recruit volunteers through the Hutch.
"My dream is that not long from now, a patient walks into a doctor's office, [the doctor] draws blood, sends the blood out for sequencing and is able to then tell the patient all the pathogens that he or she has been exposed to in the past, plus the full set of pathogens that the person's system is presently fighting," said Harlan Robins, a computational biologist at the Hutch and a co-founder of Adaptive TCR.
Robins said that in order to offer a diagnostic test based on immune sequencing, Adaptive TCR would first need to become CLIA-certified — a designation that the company is already in the process of pursuing.
The study will test for pathogens that are all highly prevalent in the Seattle population, including the herpes virus, human papillomavirus, H. pylori, chlamydia, and several fungal pathogens. Robins estimated that between 30 percent and 70 percent of the general population have been exposed to each one of the pathogens to be tested. The study will also use standard titering-based tests to determine exposure to the pathogens.
Results will not be returned to patients because "what we're measuring isn't accepted clinically as a diagnostic," Robins said. Additionally, he said, the pathogens generally do not require major medical intervention.
For each of the volunteers, the team will sequence around 10 million receptors, including both T-cell and B-cell receptors on the Illumina Genome Analyzer.
The sequencing and most of the sequence analysis will account for around one-quarter of the funding, while the titering tests will account for about one-third of the funding, with the remaining funding going towards a combination of logistics and personnel.
While a number of companies have begun to offer immune repertoire sequencing services — including Adaptive TCR, Sequenta, and iRepertoire — the study is the largest example of immune sequencing being applied clinically to date (IS 7/20/2010, 12/14/2010, and 8/31/2010).
Sequencing the immune repertoire has been challenging because it is so variable. For example, researchers at the BC Cancer Agency recently found that even among the same individual, sequencing the T-cell repertoire at two different time points yielded only a 13 percent overlap between sequences (CSN 3/22/2011).
However, researchers are increasingly interested in sequencing the immune repertoire because of the vast amount of information stored within the T- and B- cell receptors, making it an alluring technique for developing diagnostic tools.
"The adaptive immune system basically keeps a record through its immunological memory of every pathogen you've ever had or have presently," Robins said. "However, being able to read what your immune system knows has proven difficult."
Now, though, with advances in sequencing technology, Robins thinks that it can begin to be used in a clinical setting.
Sequencing would have an advantage over other methods for diagnosing exposure in that the same assay could be applied to any pathogen, he said. Furthermore, sequencing the immune repertoire would determine an array of pathogen exposures, without requiring a separate test for each.
"We hope that this truly becomes a one-stop diagnostic for a whole variety of different pathogens," Robins said.
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