NeutroTarget – Blood-Based Immune Biomarker for prognosis, prediction and monitoring of Immunotherapy Response and in Breast Cancer

A new blood-based immune biomarker to stratify and monitor cancer patients to reduce ineffective immunotherapy use.

BACKGROUND

Despite major advances in cancer therapeutics, including immune checkpoint inhibitors, triple-negative breast cancer remains challenging to treat. While immunotherapy has transformed oncology, objective response rates, particularly in advance stages, typically range between 20–40%, meaning that 60–70% of treated patients derive little or no clinical benefit.

This low and unpredictable response rate represents a major challenge for healthcare systems and payers, as immunotherapies are among the most expensive oncology treatments, often costing tens to hundreds of thousands of euros per patient. As a result, there is increasing pressure to justify patient selection, treatment continuation, and reimbursement decisions using robust predictive biomarkers.

From a drug development perspective, the lack of reliable biomarkers limits effective patient stratification and trial enrichment, leading to larger, longer, and more costly clinical trials with diluted endpoints. Current biomarkers, such as PD-L1, rely on invasive tissue biopsies, provide static information, and show limited predictive accuracy.

There is a critical unmet need for minimally invasive, scalable biomarkers that can stratify and dynamically monitor patients and improve both clinical decision-making and immunotherapy trial efficiency.

TECHNOLOGY OVERVIEW

Our research has identified a specific subset of immune cells expressing a surface receptor, present in the blood of BC patients, using standard flow cytometry. These cells are absent in healthy individuals and significantly enriched in patients with metastatic breast cancer.

The immune subset demonstrates potent immunosuppressive activity in functional assays and an enhanced ability to migrate to tumor sites, supporting a direct role in cancer progression and resistance to immunotherapy. Clinically, higher frequencies of this subset correlate with metastatic disease, fast disease progression and reduced survival.

Importantly, this biomarker can be measured at baseline and longitudinally during treatment through a simple blood draw, enabling dynamic patient stratification and treatment adjustments in real time. Its frequency informs key clinical and development decisions, including immunotherapy initiation, treatment continuation or discontinuation, therapy switching, and patient inclusion or exclusion in immunotherapy clinical trials.

By leveraging a blood-based approach rather than tissue biopsies, this technology enables real-time monitoring of immune dynamics, overcoming the static and invasive nature of current tissue-based biomarkers and supporting more adaptive clinical decision-making and trial designs.

Figure 1: Metastatic breast cancer patients have increased levels of the novel immunosuppressive subset expressing receptor X in their blood.  Percentage of immune cells expressing receptor X in the blood of non-metastatic (green bar, n =70) and metastatic (purple bar, n =72) breast cancer (BC) patients; assessed by flow cytometry. *p < 0.05.

Figure 2: Higher levels of the novel immunosuppressive subset expressing receptor X in metastatic breast cancer patients’ blood are associated with reduced life expectancy. Overall survival of BC patients with bone, liver and lung metastasis presenting either less (green line) or more (purple line) than 3% of this novel immune subset in their blood at the time it was first collected for our study.

STAGE OF DEVELOPMENT

TRL 3

Currently at the proof-of-concept stage, we are enrolling BC patients to validate the predictive value of these immune cells. Blood samples are analysed for the frequency of the subset and correlated with treatment responses. In vitro assays are conducted to further substantiate their immunosuppressive capabilities.

BENEFITS & APPLICATIONS

Primary Applications

• Patient stratification in immunotherapy clinical studies: Use as a blood-based immune biomarker to support patient selection and subgroup analyses in clinical trials of immune checkpoint inhibitors in Triple-negative breast cancer.
• Treatment monitoring during immunotherapy: Longitudinal assessment of immune dynamics during treatment to support exploratory analyses of response, resistance, or disease progression
• Prognostic assessment in metastatic disease: Identification of patients with more aggressive disease biology and poorer survival outcomes at or near the time of metastatic diagnosis.

Secondary / Future Applications (subject to further validation).

• Decision-support biomarker in clinical practice: Potential use to complement existing biomarkers in informing treatment continuation or switching decisions, pending prospective clinical validation.
• Pathway towards companion diagnostic development: Following multicenter validation and regulatory alignment, the biomarker could be further developed as part of a companion or complementary diagnostic strategy in collaboration with industry partners.

More predictive than current tissue-based biomarkers: Shows stronger correlation with metastatic disease and overall survival than PD-L1 tumor expression.

Prognostic value in metastatic disease: Demonstrates a strong correlation with the rate of disease progression and survival probability in palliative care, independent of treatment

Reduces ineffective use of high-cost immunotherapy: Enables earlier identification of likely non-responders, limiting unnecessary exposure to immune checkpoint inhibitors.

Faster, actionable results: Blood-based flow cytometry delivers rapid, repeatable data, supporting timely go/no-go and treatment adaptation decisions.

Scalable and trial-ready: Uses standard flow cytometry infrastructure, enabling consistent implementation across multi-center clinical trials and routine practice.

Enables longitudinal monitoring: Allows repeated measurements over time, overcoming the static and invasive nature of tissue biopsies.

INTELLECTUAL PROPERTY

• European patent application filed and pending, covering biomarkers for cancer monitoring, prediction of therapeutic response, and prognosis.

NOVA Inventors

Guadalupe Cabral

Bruna Correia

Rute Salvador

Daniela Grosa

Sofia Braga

António Jacinto

Telma Martins

Nídia Sousa

Diana Saraiva