Technology
Effective cancer immunotherapy relies on the recruitment and activation of cytotoxic T cells within the tumor microenvironment. The chemokines CXCL9 and CXCL10 play a central role in this process by attracting and activating CXCR3-positive T cells and supporting a positive immune feedback loop that enhances anti-tumor activity.
However, many tumors express high levels of the enzyme DPP-4, which cleaves CXCL9 and CXCL10 and converts them from active signaling molecules into inactive or inhibitory forms. This limits immune cell recruitment and contributes to resistance to therapies such as immune checkpoint inhibitors. This is particularly relevant in patients with low CXCL9/10 levels, who are less likely to respond to current immunotherapy approaches.
Patent-pending engineered CXCL9 and CXCL10 Fc-fusion variants resistant to DPP-4 cleavage overcome this limitation. These modified chemokines retain their ability to activate CXCR3 signaling and sustain immune cell recruitment within tumors, even in the presence of high DPP-4 activity.
Preclinical studies show that these variants enhance T-cell activation, increase infiltration of effector immune cells into tumors, and improve tumor growth control compared to non-modified counterparts.
By preserving and amplifying a key immune signaling pathway, this approach offers a targeted strategy to improve anti-tumor immune responses and expand the population of patients responsive to immunotherapy, particularly in settings where the tumor microenvironment suppresses endogenous chemokine activity.
Advantages
- Restores immune signaling suppressed by tumor-derived DPP-4
- Maintains biological activity within the tumor microenvironment
- Enhances recruitment and activation of effector T cells
- Demonstrates improved anti-tumor activity in preclinical models
- Designed for combination with immune checkpoint inhibitors, with potential to enhance response in non-responder populations
Applications and Opportunities
- Novel immunotherapy approach for solid tumors
- Combination therapy with checkpoint inhibitors (including emerging targets such as TIGIT) to enhance response, particularly in CXCL9/10-low tumors
- Potential solution for patients with low response to current immunotherapies
- Platform for developing protease-resistant immune-modulating proteins
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