CCL21 Cancer Immunotherapy

Abstract

Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer.

Figure 1

DC-CCL21 Immunotherapy (Left) Patient-DCs are isolated from PBMC and stimulated with 800 U/mL GM-CSF and 400 U/mL IL-4 for 6 days. Transduction with clinical grade adenoviral vector encoding CCL21 generates CCL21 secreting DCs (DC-CCL21), which are injected into patient’s tumor; (Right) DC-CCL21 cultured in fibrin hydrogel in PCL-PLCL polymer platform overnight for potential implantation in the tumor following surgical resection (proposed clinical trial for HNSCC).

Figure 2

Mechanisms of DC-CCL21 Anti-Tumor Activity Intratumoral administration of DC-CCL21 promotes chemo-taxis of naïve T cell and DC into the tumor and increases APC activity of DC leading to activation of cytotoxic T lymphocytes (CTL) but reducing activity of regulatory T cell (Treg) that culminate in tumor reduction.