Dupilumab (Dupixent)

Description

Dupilumab is a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13 signaling, originally developed and approved for allergic and inflammatory conditions such as atopic dermatitis and asthma. In colorectal cancer, dupilumab is being explored in combination with immune checkpoint inhibitors like toripalimab as neoadjuvant therapy for microsatellite stable (MSS) tumors with resectable liver metastases. The rationale is that blocking IL-4/IL-13 pathways may help overcome the immunosuppressive tumor microenvironment that typically makes MSS colorectal cancers resistant to immunotherapy.

Mechanism of Action

Dupilumab binds to the shared IL-4 receptor alpha subunit, preventing both IL-4 and IL-13 from activating their respective signaling pathways. By blocking these Type 2 inflammatory cytokines, dupilumab may reduce the recruitment of immunosuppressive cells like M2 macrophages and regulatory T cells in the tumor microenvironment, potentially enhancing the efficacy of concurrent checkpoint inhibitor therapy.

Molecular Targets

Side Effects

Not all side effects are listed. Side effects vary by individual. Always consult your oncologist.

Clinical Trials