NEW YORK (GenomeWeb News) – San Carlos, Calif.-based biotech firm Atreca said this week that it has signed a collaboration deal with Janssen Biotech and Johnson & Johnson Innovation to apply its Immune Repertoire Capture system to studies of autoimmune disease.
The aim of the project is to better characterize autoimmune disease and its progression through study of patient immune response with the ultimate goal of identifying potential drug targets, Atreca Co-founder and CEO Tito Serafini told GenomeWeb.
The collaboration will initially focus on one specific autoimmune disease, which Serafini declined to identify, with the potential to expand in the future to additional indications. Under the agreement, Atreca will receive research funding and potential milestone payments.
Launched in 2010 to commercialize technology developed in the lab of Stanford University researcher and company Co-founder William Robinson, Atreca specializes in using single-cell genomic analysis to characterize patient immune response. According to the company, its Immune Repertoire Capture platform is able to determine the sequences of full-length, natively paired antibody and T-cell receptor repertoires while also providing quantitative gene expression data that can be used to subtype and phenotype individual cells.
"What [the IRC platform] allows us to do is figure out what are the sequences of antibodies and T-cell receptors being made by individual B and T cells at high throughput," Serafini said.
By looking at the single-cell level, the collaborators aim to more precisely characterize immune responses, allowing them, for example, to identify antibodies involved in successful immune responses or track the evolution of a patient's immune response.
"This isn't averaging [based on bulk analysis of the overall immune repertoire]," said Serafini. "If I see the same antibody five times, it's because there were five individual B cells that I processed that made that antibody. And that tells us where the immune response is focusing its activity."
Such information, he noted, could be used to study a cancer patient who has responded well to checkpoint inhibitor therapy to identify the various antibodies the patient's immune system is producing with the aim of developing certain of these antibodies as potential therapeutic agents in patients suffering from the same disease.
On the other hand, the platform might be used – as in the case of the Janssen collaboration – to look at the immune response of patients with a given autoimmune disease with the aim of identifying antibodies involved in producing the aberrant immune response.
The system can also be used to track changes in the immune repertoire over time, Serafini noted, allowing researchers, for instance, to identify shifts in antibody production in response to disease progression or drug treatment.
"You can see changes in clonality in the response... and that gives you a lot of power in analyzing the immune response and extracting valuable information from it," he said.
Atreca uses next-generation sequencing to characterize antibody paired heavy and light chains. According to Serafini, the company is "platform agnostic" with regard to its choice of NGS instrument and uses several different platforms in its work.
More than NGS, Serafini said, the key technology underlying Atreca's IRC platform is the DNA-barcoding method developed by Robinson and licensed by Atreca for commercial development.
The approach uses unique oligonucleotide primers during cDNA synthesis to barcode the antibody chain sequences at the single-cell level. The barcoding system enables correction of error introduced by PCR and NGS, allowing researchers to more accurately quantify the presence of the various antibody populations. Additionally, by using negative control barcodes, researchers can detect contamination.
"The major issue is, is the output you get accurate – does it accurately reflect the composition of single cells?" Serafini said. "You are going from single-cell amounts of material all the way up to amounts of material you can throw in a sequencer, so doing that you are using reverse transcription, PCR, NGS, and there are all sorts of errors introduced by that process."
"Unless you can eliminate bias and error, you cannot precisely map out a real response," he added. "You need to know that every pair of sequences that you are looking at comes from a single cell. And when you do that you get a real representation of those single cells."
The approach is similar to that taken by genomics firm Cellular Research, which uses a barcoding system to eliminate bias and improve accuracy in single-cell mRNA and gene expression studies.
In addition to autoimmune disease, Atreca sees its technology as particularly suited to cancer immunology and infectious disease work, Serafini said. In 2012, Atreca received a $6 million dollar equity investment from the Bill & Melinda Gates Foundation which was interested in the potential of the company's technology for studying infectious disease.
One possible advantage, Serafini noted, is that it could aid in more rapidly characterizing the immune responses triggered by vaccines under development.
"The vaccine folks are very excited by this because instead of running a 10,000-patient trial they can run a much smaller trial and use our technology as an electron microscope for the immune response to try to figure out what is happening in these patients such that they can decide what to do for the next step in clinical development," he said.
In addition to its relationship with the Gates Foundation and the announced Janssen deal, Atreca, which currently has more than 20 employees, has a number of ongoing collaborations with other Gates collaborators, academic labs, and pharma companies, Serafini said. It also has ongoing internally several preclinical immuno-oncology drug development programs.
Atreca isn't alone in applying NGS to characterizing immune response. For instance, in April, Fred Hutchinson Cancer Research Center spin-out Adaptive Biotechnologies raised $105 million in private funding to expand its immunosequencing offerings.