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CCL21 gene-modified dendritic cells (CCL21-DC) are autologous dendritic cells that have been genetically engineered to express the chemokine C-C motif chemokine ligand 21 (CCL21). The primary mechanism of action involves intratumoral injection of these modified DCs to create a lymph node-like microenvironment within the tumor. This promotes recruitment and colocalization of naïve T lymphocytes and antigen-experienced DCs, enhancing local and systemic antitumor immune responses by facilitating T cell activation. Preclinical studies demonstrated increased infiltration of CD4+, CD8+ T cells, and endogenous DCs into tumors following treatment. Clinically, phase I trials in advanced non-small cell lung cancer (NSCLC) have shown feasibility, safety, induction of tumor-specific immune responses, and disease stabilization in a subset of patients. The therapy is also being investigated in combination with pembrolizumab (anti-PD-1 antibody) to potentially overcome resistance to checkpoint inhibitors.
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