Chemokine
A subclass of cytokines that direct the migration of immune cells to sites of inflammation or infection. CXCL12 (SDF-1) is a chemokine that binds the CXCR4 receptor to retain stem cells in bone marrow. Motixafortide blocks CXCR4, mobilising stem cells into the bloodstream.
Technical Context
Chemokines are classified by cysteine motif: CC chemokines (CCL1-28, receptors CCR1-10 — recruiting monocytes, lymphocytes, eosinophils), CXC chemokines (CXCL1-16, receptors CXCR1-6 — recruiting neutrophils, lymphocytes), CX3C chemokines (CX3CL1/fractalkine, receptor CX3CR1), and C chemokines (XCL1-2, receptor XCR1). CXCL12 (SDF-1) and its receptor CXCR4 are the most therapeutically relevant chemokine axis in peptide pharmacology: CXCL12/CXCR4 retains haematopoietic stem cells in bone marrow niches, regulates immune cell trafficking, and plays roles in cancer metastasis (many tumours express CXCR4 and are attracted to CXCL12-rich tissues). Motixafortide is a cyclic peptide CXCR4 antagonist that blocks the CXCL12/CXCR4 interaction, mobilising stem cells from marrow. Beyond stem cell mobilisation, CXCR4 antagonism is being investigated for: enhancing immune checkpoint inhibitor efficacy (by increasing T cell tumour infiltration) and blocking cancer metastasis.