T cell checkpoint inhibitors have led to positive clinical outcomes in a range of cancers, yet most patients do not respond. New approaches are urgently needed. The Siglec-Sialoglycan axis is a previously underappreciated mechanism of immunosuppression that has recently emerged as a major tumor immune escape pathway. It modulates NK cell, macrophage, dendritic cell, and T cell functions concurrently. Inhibiting the Siglec-Sialoglycan axis offers the potential to activate both innate and adaptive anti-tumor immune responses and treat patients who do not respond to T cell checkpoint therapies.
Targeting the Siglec-Sialoglycan axis is challenging with conventional approaches to drug development. Palleon has developed a suite of technologies to address this significant but highly complex opportunity.
The Science of Glyco-Immunology
Learn more about Siglecs and their role in immunosuppression
The Siglecs are a family of receptors found on innate immune cells such as macrophages, dendritic cells, and NK Cells, as well as adaptive immune cells including effector memory T cells. The Siglecs inhibit immune cell activation after sensing certain sialic acid-containing glycan patterns, or sialoglycans. Tumors take advantage of these sialoglycan-sensing checkpoints by evolving to express hypersialylated cell surface glycan patterns, which engage Siglecs on innate and adaptive immune cells, resulting in a broad, comprehensive suppression of the anti-tumor immune response.
Targeting the Siglec-Sialoglycan axis of immunosuppression offers two distinct advantages over other immuno-oncology efforts. First, since glycan-mediated immunosuppression affects the full range of innate and adaptive immune cells required for a robust anti-tumor immune response, drugs that target this axis have the potential to overcome resistance to T-cell checkpoint therapies. Second, tumor glycan patterns can be identified, providing insights on which patient populations are most likely to respond to treatments targeting the Siglec-Sialoglycan axis.