Development of Diagnostics for Autoimmune Diseases Based on Sequencing T-Cell Signatures
Adaptive Biotechnologies, a commercial-stage biotechnology company, has initiated a research project with Finnish biobanks and Finnish Biobank Cooperative - FINBB to utilize Finnish biobank samples for development and validation of immunosequencing-based clinical testing for autoimmune disorders, such as inflammatory bowel diseases (IBD).
Background
Autoimmune diseases are a group of conditions caused by malfunction of the adaptive immune system. Common autoimmune disorders such as inflammatory bowel diseases (IBD), like Crohn’s disease (CD) and ulcerative colitis (UC) have the highest prevalence and incidence in North America and Europe (Scott et al. 2010, Ananthakrishnan 2015). Even though considered relatively uncommon, the effects of these diseases on mortality, morbidity and health economic burden are significant (Wang et al. 2015). The majority of testing in autoimmune diseases has utilized serology to measure the presence of antibodies, but often lacks specificity for the disease or the ability to measure changes in disease state. Until recently, T-cell responses have been more difficult to measure at a population level than antibodies, although they can provide a more accurate diagnosis.
T cells rearrange portions of their receptor sequences in order to generate a vast repertoire of “signatures” capable of detecting any possible pathogen and play an integral role in coordinating the adaptive immune response against many pathogens, including cell-mediated and antibody responses. T-cell receptors (TCR) recognize foreign antigens from pathogens and, in a manner that can be protective or destructive, variations on self-antigens in cancer and autoimmune diseases. Despite the overwhelming number of possible TCRs, some TCR sequences are shared between individuals with the same disease or who have been exposed to the same antigen, titled public TCRs. If we can read a patient’s T-cell repertoire and know the identity of the TCRs involved in a specific disease, then the information encoded in these receptors can finally be clinically useful.
When specific TCR sequences associated with particular antigens or disease states are known, scanning the T-cell repertoire for those specific sequences is clinically useful. Adaptive Biotechnologies has developed a platform for sequencing T- and B-cell receptors at-scale, including the immunoSEQ® Assays for research to study, track, monitor, and quantify the adaptive immune response. The immunoSEQ Assays utilize next-generation sequencing (NGS) to identify the rearranged immune receptor sequences accurately and quantitatively. immunoSEQ can be used to determine the diversity of the adaptive immune system, track specific clones and identify public or private responses in health and disease. By studying large cohorts of patients with a certain disease we can identify public TCRs to build out the capabilities for the development of clinical tests to improve diagnosis and disease monitoring.
For more information on immunoSEQ, visit https://www.immunoseq.com.
Objective
Presently, Adaptive is using immunoSEQ to generate large datasets of TCR sequences specific for different autoimmune diseases. In partnership with Microsoft, Adaptive is combining their immunoSEQ Assays with Microsoft’s machine learning expertise to identify clinically useful public TCR signatures. The objective is to utilize this underlying technology to develop blood-based diagnostics that will detect autoimmune diseases at an earlier stage than is currently possible or available, shortening the diagnostic odyssey and allowing for disease monitoring. Adaptive recently launched and received emergency use authorization from the FDA for their first T-cell-based clinical test, T-Detect™ COVID for confirming recent or prior COVID-19 infection.
Purpose of the Study with Finnish Biobanks
With FINBB, Adaptive is working with biobanks across Finland to study a large number of additional blood samples to discover and validate TCR signatures specific to a number of diseases of interest. For this phase of the study, samples from CD, UC, and irritable bowel syndrome (IBS) were identified in Finnish public biobanks through the Fingenious® service managed by FINBB. Samples from over 2,000 sample donors at Auria Biobank, Helsinki Biobank and Biobank of Eastern Finland are being prepared for shipping to Adaptive for immunoSEQ analysis.
“Working with FINBB through Fingenious has allowed us to identify useful cohorts of patient samples across a range of diseases,” says Ian Kaplan, associate director of partnerships at Adaptive Biotechnologies. “FINBB’s collaborative team and expansive bank of samples is helping us to identify T-cell signatures for autoimmune disorders for our T-Detect pipeline of tests.”
”Public-private partnership with R&D focused innovative pharmaceutical companies like Adaptive Biotechnologies Corporation is crucial so that the Finnish biobank services can be utilized for the good of patients. We are happy that this unique research cooperation can speed up the transfer of data from research to patient care”, says Marco Hautalahti, CEO of FINBB.
References
Ananthakrishnan (2015) Nat. Rev. Gastroenterol. Hepatol. 12, 205–217
DeWitt et al. (2018) eLife. 7, e38358
Scott et al. (2010) Lancet. 376, 1094–1108
Venturi et al. (2008) Nat. Rev. Immunol. 8, 231–238
Wang et al. (2015) J. Intern. Med. 278, 369–395
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Adaptive Biotechnologies Corporation is a commercial-stage biotechnology company focused on harnessing the inherent biology of the adaptive immune system to transform the diagnosis and treatment of disease. Adaptive believes the adaptive immune system is nature’s most finely tuned diagnostic and therapeutic for most diseases, but the inability to decode it has prevented the medical community from fully leveraging its capabilities. Their proprietary immune medicine platform reveals and translates the massive genetics of the adaptive immune system with scale, precision and speed to develop products in life sciences research, clinical diagnostics and drug discovery. Adaptive has three commercial products and a robust clinical pipeline to diagnose, monitor and enable the treatment of diseases such as cancer, autoimmune conditions and infectious diseases. The company’s goal is to develop and commercialize immune-driven clinical products tailored to each individual patient.
Finnish Biobank Cooperative - FINBB is a biobank cooperative founded and owned by six largest hospital districts and universities and Finnish Institute for Health and Welfare (THL). All public biobanks are members of FINBB. FINBB coordinates the operations of the biobank network in Finland and aims to create an internationally advanced biobank infrastructure. FINBB has a significant role of Finnish National Health Sector Growth Strategy implementation and internationalization. FINBB’s Fingenious® service is the digital gateway to Finnish biobanks and biomedical research.