Oxford BioDynamics part of consortium shortlisted for Strategic Government Initiative to Improve Cancer Immunotherapy
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CIRRP is a £9M initiative aimed at putting the
UK at the forefront of cancer treatment, that was announced by TheMedical Research Council and theOffice for Life Sciences , part of theDepartment of Health and Social Care and theDepartment for Science , Innovation and Technology earlier this year. - CIRRP aims to enhance the benefits, and navigate the complexity of cancer immunotherapy using PD-1/PD-L1 antagonists by addressing the low and variable response rates to therapy as well as predicting severe side effects.
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Oxford BioDynamics has formed a consortium with world leading experts in molecular epigenetics at the
University of Oxford , in clinical metabolomics and lipidomics at theUniversity of Birmingham , and in cancer treatment withImperial College Healthcare NHS Trust andNorfolk andNorwich University NHS Trust . -
The consortium submitted a proposal to advance immunotherapy in
NHS patients diagnosed with five of the most prevalent cancers using Oxford BioDynamic’s EpiSwitch® CiRT and HiRT to predict both response to ICIs and their potential side effects as well as discover the underlying mechanisms behind different response rates. - The consortium’s proposal has been shortlisted for award consideration.
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The EpiSwitch® Checkpoint Inhibitor Response Test (CiRT) is the first in class, blood-based, accurate predictor of response to ICIs. The test is commercially available through clinical diagnostic labs in the US and
UK . -
The EpiSwitch® Hyper Immune Response Test HiRT is a unique prognostic blood test designed on the EpiSwitch platform with support from the
Partnership for Accelerating Cancer Therapies (PACT, USA ). The test accurately predicts individuals most likely to exhibit hyperprogressive disease (HPD), a response to immunotherapy which triggers life threatening, disease accelerating side effects. An average of 12% of ICI-treated patients exhibit HPD. -
If the consortium’s proposal is successful,
NHS patients with colorectal, prostate, breast, ovarian or lung cancer would be prospectively evaluated with CiRT and HiRT, and together with their clinical outcomes and individual genetic, epigenetic and metabolic states used to offer mechanistic insights into their immune systems and clinical outcomes.
The proposal to CIRRP is a public/private partnership which will involve clinicians and academics from the Universities of
In the proposal to the
If the proposal is accepted, the consortium will:
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Establish the CIRRP platform within an existing OBD ISO15189/UKAS accredited clinical laboratory to offer
UK -based EpiSwitch CiRT and HiRT clinical screening on at least 350 patients - in prostate, colorectal, breast, ovarian and lung cancers, initially at theNHS trusts within the consortium, and then acrossNHS networks across theUK , using an established transparent cost per patient sample model. -
Create real-world impact data within
NHS clinical practice for prediction of ICI response and prognosis of Hyperprogressive disease (HPD). The initial focus will beNHS patients considered for or currently receiving anti-PD-1 or anti-PD-L1 ICI treatment for prostate, colorectal, breast, ovarian and lung cancers. Understanding the distinct Objective Response Rate to ICIs means precise understanding of rates of response/non-response to treatment, immune-related adverse events (irAEs) or HPD becomes critical. - Advance the understanding of genetic, metabolomic and epigenetic mechanisms behind clinical outcomes, acquired resistance and remission. The world-class expertise of the research team will be guided through the multiomic complexity of genomes by focusing on the functional genomic footprints of networks of 3D EpiSwitch biomarkers strongly associated with clinical outcomes of ICI treatments.
EpiSwitch® Checkpoint inhibitor Response Test (CiRT)
Cancer does not exist in isolation. The most successful approaches for treating cancer will need to consider the larger systemic picture, comprising a combination of the tumour, its interaction with its environment, the immune system, and a patient’s genome and epigenome.[1,2] Most current predictive biomarker tests focus on specific genetic markers such as (i) tumour mutation burden (TMB), which measures the extent of DNA mutations in a tumour acting as a proxy for how readily an engaged immune system may recognize the tumour, or (ii) protein markers, such as expression of PD-L1 protein in the tumour, a direct target of ICI. These tests rely on retrieving a biopsy or resections from a tumour, but these tumour-based methods show limited success at predicting who will benefit from ICI treatment. A recent retrospective analysis that systematically evaluated all clinical trials leading to FDA approvals of ICIs from 2011 to 2019, found that the most studied marker, tumour PD-L1 expression, was predictive in only 24.4% of cases.[1,2] Unfortunately, the data does not support either tool as a good predictor of response to ICI treatment, as ICIs reset the immune system of the host to fight the cancer and they do not directly target the tumour.
The EpiSwitch® CiRT is a first-of-its-kind blood test that accurately predicts an individual cancer patient's therapeutic response to immune checkpoint inhibitors (ICIs), providing unique benefits for physicians in treatment planning and navigating complex decisions.[3,4] ICIs offer a real hope of durable disease control for some patients. Despite pre-screening with current standard tests such as tumor PD-L1 expression, these ICIs offer a long-term survival advantage to less than 1 in 4 patients, and many may become seriously ill and require hospital admission.
An important consideration is the high cost of treatment with an ICI. The anti-PD-1 and anti-PD-L1 therapies represent some of the most expensive therapies employed today. In order to allow equitable access by
EpiSwitch Hyper-progressive Immune Response Test (HiRT)
Treatment with an ICI elicits a spectrum of side-effects and immune related adverse events, including a subgroup of patients with hyperprogressive disease (HPD). HPD patients demonstrate significantly reduced progression free survival (PFS<2mo) and overall survival (OS<5mo), with increased tumour growth rates and underlying molecular trends of genomic amplifications (MDM2, etc.) and lesion accumulation. A retrospective analysis of 24 studies and 3,109 patients revealed that the incidence of HPD varies from 5.9% to 43.1% across different cancers, with an average of 12%.[5]
With a special award from the
Dr Alexandre Akoulitchev, CSO at OBD, said: “The EpiSwitch platform and its systemic biomarkers have already delivered the most accurate test, as of today, for predicting response to ICIs treatment – CiRT. The test has been adopted by a growing number of institutions and practicing clinicians, and patients in the
“The other benefit our consortium is offering is the power of the EpiSwitch platform to capture the systemic aspects of cancer biology. With the guidance from our academic and clinical world-class experts, we can combine genetic, epigenetic and metabolic specifics of every patient. We can gain insights into predispositions to immune related adverse events (irAEs), side effects to immune oncology treatment. Their burden is significant and should not be overlooked. The CIRRP initiative is focused on the challenge that could propel the
Professor
References
[1] Hunter, E., et al. (2023). Development and validation of blood‐based predictive biomarkers for response to PD‐1/PD-L1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications, Cancers 15(10), 2696. https://www.mdpi.com/2072-6694/15/10/2696
[2] Zhao, B.; Zhao, H.; Zhao, J. (2020). Efficacy of PD-1/PD-L1 blockade monotherapy in clinical trials, Therapeutic Advances in Medical Oncology, Vol. 12. https://doi.org/10.1177/1758835920937612
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[4]
[5] Park, H. J.; Kim, K. W.; Won, S. E.; Yoon, S.; Chae, Y. K.; Tirumani, S. H.; Ramaiya, N. H. (2021). Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease during Cancer Treatment with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis, JAMA Network Open, Vol. 4, No. 3. doi:10.1001/jamanetworkopen.2021.1136
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