Neutrophil Subsets for the Treatment of Cancer

THE CHALLENGE

Developing a cancer immunotherapy platform that can effectively and safely leverage the complex role of neutrophils—an abundant, yet highly variable, type of innate immune cell continues to prove challenging. Unlike current therapies that primarily target the adaptive immune system, an approach that must navigate the dual nature of neutrophils, which can either suppress or support anti-tumor activity depending on their phenotype. Technically, this involves overcoming significant hurdles in identifying and isolating specific pro-inflammatory or tumor-fighting neutrophil subsets, while avoiding unintended side effects like systemic inflammation or immune suppression. The lack of precision tools and standardized methods to modulate these cells has stymied drug development, creating a critical need—and significant market opportunity—for innovative solutions that can reliably control neutrophil behavior and improve outcomes in cancer patients.

OUR SOLUTION

We offer a groundbreaking immunotherapy platform that reprograms innate neutrophils into immune-enhancing cells through a controlled ex vivo priming process, addressing a critical gap in current cancer treatments that largely ignore the innate immune system. By using precise, low-dose combinations of GM-CSF or G-CSF with lipopolysaccharide (LPS), we induce a targeted phenotypic switch that selectively expands a beneficial subset of neutrophils—marked by low CD177 and high Dectin-2 (CLEC4N) or EHD1 expression—with strong immune-stimulating potential. These reprogrammed cells, isolated via established techniques like flow cytometry or magnetic bead separation, are formulated for intravenous delivery to reshape the tumor microenvironment and boost anti-tumor immune responses. This platform presents a highly differentiated, first-in-class approach that could complement or enhance existing immunotherapies, offering strong potential for partnerships, licensing, or clinical development in the rapidly growing cancer immunotherapy market.

Single cell RNA sequencing (scRNAseq) analyses of murine neutrophils showing differentially expressed genes, revealing the nature of immune-enhancing neutrophils capable of enhanced anti-tumor immune defense.  Purified naïve mouse bone marrow neutrophils or neutrophils treated with low-dose LPS (100 pg/ml) in the presence of GM-CSF (1ng/ml) were used to perform single cell sequencing.  Differentially expressed genes were identified in the above bubble plot.

Advantages:

• Broad-spectrum tumor targeting via reprogrammed innate neutrophils
• Scalable, cost-effective manufacturing using readily available donor cells
• Precise cell selection with unique biomarkers (CD177lo, Dectin-2hi, EHD1hi)
• Compatible with combination therapies for enhanced treatment outcomes

Potential Application:

• Intravenous cancer immunotherapy using reprogrammed neutrophils
• Adoptive cell transfer therapy for solid and hematological tumors
• Combination therapy with checkpoint inhibitors or chemotherapeutics
• Preventive immunomodulation in high-risk or immunocompromised patients