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The development of a predictive biomarker for immunotherapy outcome based on flow cytometry test

Project description

Neutrophils: can they predict immunotherapy outcome?

The immune system has many ways of regulating the strength of immune responses such as checkpoint proteins which have an inhibitory role on T cell function. Inhibiting these checkpoint proteins represents an immunotherapy strategy designed to elicit anti-tumour responses. However, this type of immunotherapy exhibits limited clinical success with no clear evidence of the underlying etiology. Funded by the ERC, the BioFlow project capitalises on the discovery of a subpopulation of neutrophils as a biomarker for immune checkpoint inhibitor therapy. With these cells being present in responsive tumours, they offer a powerful tool for predicting response to therapy and also improve the design of future immunotherapy strategies.

Objective

Immunotherapy has revolutionised clinical oncology, with the use of immune checkpoint inhibitors (ICIs). These agents are in clinical use for almost a decade, treating over 20 types of cancers. They have shown a remarkable therapeutic benefit even in patients with advanced disease. Yet, only a small proportion of patients benefit from this therapy, leaving the rest resistant, for reasons that are still not clear. While there are certain clinical biomarkers to predict ICI therapy outcome, their prevalence and prediction power is rather limited. Therefore, there is a clinical unmet need to develop more powerful biomarkers to predict response to immunotherapy. In our ongoing ERC consolidator grant we discovered a unique sub-population of neutrophils, present in peripheral blood, that predicts response to immunotherapy in a very high probability. We designated these cells as immunotherapy-responsiveness cells (IRCs). Using various mouse models, we demonstrate that the levels of circulating IRCs measured at baseline are significantly higher in responding tumours to ICI therapy. These results were confirmed in a limited number of non-small cell lung cancer (NSCLC) and melanoma patients. Hence, our aim is to further test IRC levels in clinical samples, to evaluate their predictive power for ICI therapy, and to develop a clinical liquid biopsy-based predictive biomarker using flow cytometry test. The development of clinical IRC detection based on flow cytometry (BioFlow®) can serve two markets: (1) Clinicians – enabling oncologists to easily predict response to ICI therapy, thus improving personalised immunotherapy treatment; and (2) Pharmaceutical companies - developing immunotherapies - that can use IRC detection in development stages and through clinical studies, enabling tight regulative assessment of R&D success rates. The BioFlow goal is to technically validate and develop a predictive biomarker platform for both markets that will lead to its commercialisation.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC2

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Host institution

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
SENATE BUILDING TECHNION CITY
32000 Haifa
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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