Chemokine-Based Immunotherapy: Delivery Systems and Combination Therapies

Abstract

A major role of chemokines is to mediate leukocyte migration through interaction with G-protein-coupled receptors. Various delivery systems have been developed to utilize the chemokine properties for combating disease. Viral and mutant viral vectors expressing chemokines, genetically modified dendritic cells with chemokine or chemokine receptors, engineered chemokine-expressing tumor cells and pDNA encoding chemokines are among these methods. Another approach for inducing a targeted immune response is fusion of a targeting antibody or antibody fragment to a chemokine. In addition, chemokines induce more effective antitumor immunity when used as adjuvants. In this regard, chemokines are codelivered along with antigens or fused as a targeting unit with antigenic moieties. In this review, several chemokines with their role in inducing immune response against different diseases are discussed, with a major emphasis on cancer.

Cell-Cell Communication in the Tumor Microenvironment, Carcinogenesis, and Anticancer Treatment

“…It operates within very tight regulatory mechanisms, as its activation brings about severe cell and tissue damage. Another antibody immunotherapy approach is to block a ligand from its interaction with a receptor or from serving as a payload for more conventional anticancer treatments such as chemotherapy or radiation [260]. Examples for approved antibody immunotherapy are monoclonal antibodies that bind such proteins as the B-lymphocyte antigen CD20 (ibritumomab tiuxetan, ofatumumab, and rituximab); the cell membrane receptor CD30, or TNFRSF8, (brentuximab vedotin); the transmembrane receptor CD33, or Siglec-3, (gemtuzumab ozogamicin); CD52 (alemtuzumab); the cytotoxic T-lymphocyte antigen 4 CTLA-4 (ipilimumab); the epidermal growth factor receptor EGFR (cetuximab, panitumumab); vascular endothelial growth factor VEGF (bevacizumab); and HER2/neu receptor (trastuzumab).…”

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

“…The process of DC maturation occurs simultaneously with an upregulation of the chemokine receptor CCR7 (Forster et al, 2008), which directs mature DCs to different lymphoid compartments where a gradient of CCL19/21 is present (Randolph et al, 2008). The functions of specific chemokine receptors on DCs and their ligands have been previously reviewed (Mohit and Rafati, 2012) and will not be repeated here. The process of chemokine receptor modulation on blood DCs and their precursors drives inflammatory influx into tissues.…”

Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma

“…Mutated genes in NAFLD-HCC were enriched in eight important cancer pathways while mutations in lean HCC only involved in two of these pathways as revealed by KEGG pathway enrichment analysis (Figure 2b). In NAFLD-HCC, mutations laid on genes involved in Calcium signaling pathway, which regulates a broad range of cellular events including those important in tumorigenesis; 25 Gap junction, which participates in the regulation of cell growth and differentiation; 26 focal adhesion, which has important roles in cell motility, proliferation, differentiation and survival; 27 GnRH signaling, which functions in regulating cancer proliferation, metastasis and angiogenesis; 28 chemokine signaling, which is involved in tumor survival, metastasis and neovascularization; 29 MAPK signaling, which participates in cell proliferation, differentiation and migration 30 and two well-known cancer-related pathways, cytokine–cytokine receptor interaction and pathways in cancer. On the other hand, only MAPK signaling and pathways in cancer were significantly affected by mutations during HCC development in lean mice.…”