The Immunobuddies Podcast discusses benefits of CiRT for immunotherapy

Last updated: 28 October 2024

In episodes 107+108+109 of "The Immunobuddies" podcast, hosts Dr. Ricky Frazer and Dr. Anna Olsson-Brown lead an insightful discussion on the benefits offered by the EpiSwitch® CiRT blood test from Oxford BioDynamics. The first episode, titled "Can We Predict Response to Immunotherapy?", is part of a three-episode series including special guests Dr. Ryan Mathis and Dr. Bartu Ahiska, from Oxford BioDynamics, that explains how the EpiSwitch CiRT blood test stands out by evaluating a cancer patient’s immune system readiness to work with checkpoint immunotherapy to fight their cancer.

Dr. Ricky Frazer is a Medical Oncology Consultant and clinical lead working at Velindre Cancer Centre (VCC) in Cardiff. He specialises in renal cancer, skin cancer and acute oncology, is a founding member of the UK Renal Oncology Collaborative (UK ROC), Vice President of the National Immuno-Oncology Clinical Network (IOCN), and co-leads the monthly National Immuno-Oncology Education Forum.

Dr. Anna Olsson-Brown is also a Medical Oncology Consultant specialising in the systemic treatment of skin cancers; sarcoma; immunotherapeutic toxicities, and early phase/translational clinical trials. She is Clinical Director for the Acute Division at the Clatterbridge Cancer Centre Liverpool, Honorary Senior Lecturer at the University of Liverpool, and also a founding member and current CEO of the National Immunotherapy Clinical Network (IOCN), sitting on the UK Chemotherapy Board within this role. Within Clatterbridge she is the Chair of the Immunotherapy Committee and Deputy Chair of Supportive Care SRG, and current Clinical Advisor to Health Education England and the British Medical Journal.

The Immunobuddies podcast series, which focuses on the challenges and progress made in the management of cancer patients receiving immunotherapies, has previously talked at depth about how current tumour-based biomarkers try to predict response to a class of widely-used immunotherapy drugs called immune checkpoint inhibitors (ICIs). The discussion includes the challenges of trying to interpret and translate scores given by PD-L1 expression and Tumour Mutational Burden (TMB) into a prediction of how likely a particular patient is responding to treatment.

"We haven't really got a good group of things that we can put together to create a (response) score at the moment, so we can't stratify patients in the way that we want to. We have got things that we think suggest that there'll be more of a chance of response or toxicity… but at the moment we can't say to a patient this is these are the things that make up your stratified response and therefore you are likely to get a benefit and likely to get toxicity”, says Dr. Anna Olsson-Brown. "It's really difficult to turn it into a personalised score or personalised tool from the information that we've got and the markers of what we think give us a trend towards benefit. We just aren't there. We don't necessarily know all of the factors that are involved. We don't necessarily know how to measure all of those and we certainly don't have a way of predicting that per patient at the moment."

EpiSwitch CiRT, a test currently available privately in the US and UK and covered by Bupa UK insurance, aims to fill this gap. CiRT is a unique predictive test in a number of different ways. As Dr. Ryan Mathis explains, firstly, everything that has come before is predominantly tumour-based. Whereas what EpiSwitch CiRT looks at is the immune system's "fitness," or how it is primed, to respond to an anti-PD-L1 or PD-1 ICI therapy. It's a highly accurate peripheral blood test that looks at 3D genomic folding patterns within the circulating lymphocytes and neutrophils of the patient.

“What we've been able to do is find key anchor points in the DNA that gives us a genetic signature that enables us to answer the question for immune checkpoint inhibitors, specifically PD-L1 and PD-1, whether somebody has a High Likelihood or a Low Likelihood of response. And by looking at it epigenetically, we actually are able to create a test that doesn't have to steal from Peter to pay Paul, but can be both highly sensitive and specific, has an accuracy of 85%, a sensitivity of 93%, and a specificity of 82%," says Dr. Ryan Mathis. “What's most exciting about it is it has a negative predictive value (NPV) of 97%. It does a really good job of telling you whether or not a patient is not going to respond to immunotherapy.

This compelling performance statistic is particularly important because administering an ICI is not an indolent therapy. It comes with its risk profile and the potential for serious side effects. "Are (checkpoint inhibitors) the biggest breakthrough in cancer in the past decade? Absolutely. But it's not perfect. Still, with the modalities that you mentioned earlier (PD-L1 expression and TMB), even in the best non-cutaneous cancers, there's an overall response rate at most 30%. This CiRT technology really got me excited because ICIs have become so frequently used around the world, and it's actually an expensive therapy and not indolent."

What follows is a deeper dive into the epigenetic signal that is measured by the EpiSwitch CiRT test. All DNA is, very intentionally, rolled up and highly compacted into the nucleus of a call. How this DNA is folded switches whether the DNA will go through the transcription process. It carries critical, powerful health information that is stable and conserved between cells, but which can change depending on the immune system's interactions with a tumour microenvironment. The CiRT test robustly measures the presence or absence of eight specific distinct 3D-genomic folds in crucial regulatory region associated with immunotherapy response, giving us an idea at a single time point whether a patient is going to be High Likelihood or Low Likelihood.

Another benefit of adopting the CiRT test is its systemic view of the problem by sampling peripheral blood. “We talk a lot about things like tumour heterogeneity, and the fact that, if we biopsy the wrong bit of tumour, we'll get a different PD-L1 status, and therefore, how do we interpret this?" says Dr. Ricky Frazer.

“This is a fascinating area of oncology for me because I feel like it's a missing piece, just like sort of how everybody else is looking at the tumour, nobody's looking at the immune system,” replies Dr. Ryan Mathis. "(Former methodologies) are looking at only who we're fighting; they don't really know who's behind us and how helpful they'll be. But (CiRT is) bringing the patient to the therapy rather than bringing the therapy to the patient. Having them meet."

Next week, the second of three podcasts covering EpiSwitch CiRT will pick up how the test is being used, and the direction that response prediction is headed. Stay tuned.

The Immunobuddies podcast is widely available to stream on-demand across the major podcast platform, including on Apple Podcasts , Spotify , and Buzzsprout