High-Precision T-Cell Testing: Driving Diagnostics Forward
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The COVID-19 pandemic and the recent rise in global cases of monkeypox and other infectious diseases have brought human immunology into the spotlight. Understanding how our bodies fight invaders and how this response can be measured is important for the development of effective diagnostics, vaccines and therapeutics. While the focus on the human body’s response to pathogens often centers around the role of antibodies, T cells are also crucial to this process. T-cell testing can therefore provide scientists with an abundance of information that can be used to detect and monitor a range of diseases as well as guide therapeutic development.
To learn more about T-cell testing, the types of diseases it can help to diagnose and its value in clinical trials, we spoke to Phill Keefe, chief executive officer of PerkinElmer’s Oxford Immunotec division. In this interview, Phill also shares his thoughts on how high-precision T-cell testing could be improved in the future.
Anna MacDonald (AM): What role do T cells play in the immune system, particularly in fighting infections?
Phill Keefe (PK): The human body’s immune system is comprised of two branches: innate immunity and adaptive immunity. While innate immunity is the body’s first line of defense against pathogens – mounting a general response to invading cells – adaptive immunity is a bit slower and much more specific. This is the branch of immunity that T cells belong to.
The adaptive immune system is comprised of both cellular (or T cell) immunity and humoral (or B cell) immunity. Developed from stem cells in the bone marrow, T cells multiply and differentiate into helper, regulatory or cytotoxic T cells, each of which have different roles in the immune response. These various T cells migrate into peripheral tissues or circulate in the blood or lymphatic system to help respond to virtually any antigen and fight infections.
In the past, including in the early days of the COVID-19 pandemic, T cells were often overlooked as a monitoring device for the immune response in favor of antibodies. However, extensive research carried out into immune responses to SARS-CoV-2 has demonstrated the importance of T cells in protecting us from disease, as well as the critical role that they can play in measuring immune responses to infection.
AM: Can you describe methods most commonly used to measure T-cell response to infectious diseases?
PK: Recent evidence suggests that the measurement of T cells can provide beneficial insights into the ability of individuals to mount an effective, durable immune response following natural infection or vaccination. One method for conducting these assessments is with an enzyme-linked immunosorbent (ELISA) assay. ELISAs rely on plates coated with “capture” antibodies that bind to specific cytokines and quantify their concentration in sera of infected patients, or in supernatants from blood or peripheral blood mononuclear cells (PBMCs) stimulated with pathogen peptides. ELISAs are simple to implement and widely commercially available.
Then there are enzyme-linked immune absorbent spot (ELISPOT) assays, which are well known and often used in the field of functional quantification of antigen-specific T cells. Rather than measure concentration, a highly sensitive ELISPOT assay will isolate T cells and interrogate them in vitro to identify those rare T cells that produce the chemical messenger in response, identifying them as being specific for the infection. This is the category that Oxford Immunotec’s T-SPOT® technology falls into.
AM: What types of infectious diseases can T-cell testing help diagnose?
PK: In addition to aiding in the diagnosis of respiratory illnesses like COVID-19, T-cell testing is incredibly impactful in the detection and diagnosis of tuberculosis (TB), which is the second leading cause of death by infectious disease globally, only behind COVID-19.
According to the 2022 World Health Organization (WHO) TB report, there were approximately 1.6 million TB deaths in 2021 – an increase from the estimated 1.5 million in 2020. In addition to this, the 2022 report estimated that 10.6 million people fell ill with TB in 2021, an increase from 10.1 million in the 2021 report. This tells us that not only does TB remain a pervasive global health problem, but that it continues to spread at an alarming rate. Better access and more widespread use of all diagnostic tools able to detect active and latent cases of TB will be essential in the coming years.
In addition to infectious diseases, T-cell measurement can be implemented to monitor autoimmune and inflammatory diseases, guide therapeutic choices, aid in the development of new cancer treatments and in transplant medicine.
AM: Why are vaccine developers incorporating T-cell testing into their clinical trials? What value does this offer?
PK: Gathering data about a patient’s adaptive immune response helps vaccine manufacturers understand the efficacy of their product. This insight is essential during every step of phased clinical trials and while working toward regulatory approval. However, obtaining this very specific data can be challenging to scale as trials expand.
Oxford Immunotec had the opportunity to provide T-cell testing for SARS-CoV-2 vaccine research with the UK Vaccine Task Force (VTF) that was established in 2020 to expedite the production of a coronavirus vaccine. Our experience with this collaboration demonstrated growing demand in access to quality T-cell testing for larger throughput volumes. As a result, our business formally launched global immunology testing services to offer our team’s expertise to vaccine and immunotherapy manufacturers involved in phased clinical trials.
AM: Is there room for continued improvement in high-precision T-cell testing?
PK: Diagnostics developers, whether focused on assays for T-cell measurement or not, are continuously innovating to improve upon their offerings. The challenge is to ensure that any modifications made to a test maintain the original assay’s sensitivity and specificity. This is especially true in non-research applications, as even the slightest changes may need to undergo regulatory approval. Automation, especially when applied in the larger workflow, is where there is perhaps the greatest opportunity for improving the scalability, efficiency and reliability of high-precision T-cell testing.
Today’s solutions for laboratory automation essentially allow labs to do more with less. Especially against the backdrop of today’s lab personnel shortage, fully automated instruments have the ability to maximize throughput while freeing up technicians for more sophisticated tasks where their expertise is needed – all without compromising accuracy required to make critical, time-sensitive clinical decisions. Oxford Immunotec’s recent FDA approval of the T-Cell Select reagent is used to automate the isolation of immune cells from peripheral blood samples using positive immunomagnetic selection.
AM: Where can we learn more about advances in this area of diagnostics?
PK: This is an incredibly dynamic and exciting field of science, and we expect continued research efforts to shed light on other ways high precision T-cell testing is being put into practice. Non-government organizations and organizations like the World Health Organization are excellent resources in this field of study. FIND | Diagnosis for all (finddx.org) is also a great resource for innovation in diagnostics in general, with a particular focus on improvements in access to the best diagnostics.
Oxford Immunotec have also worked with T-cell experts from around the globe to develop a range of resources that provide information on the role of T cells in infectious diseases, immunology and vaccine development. Visit Educational Content – tcellexperts.com to view the educational content.
Phill Keefe was speaking to Anna MacDonald, Interim Managing Editor for Technology Networks.