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G. Yang and Y. Huang
6.4.4 Other Inflammatory-Associated Factors
6.4.4.1 Hepcidin
A 44 nt L-type RNA aptamer NOX-H94 binds to human iron metabolism regulator
hepcidin, thereby preventing hepcidin-induced iron port protein degradation and
ferritin expression [168]. Inhibiting hepcidin is an efficient path of chronic inflammatory anemia therapy. In a pharmacodynamic study of healthy individuals, NOX-H94
blocked the effect of hepcidin on serum iron levels. Recently, two phase 2 evaluations
of NOX-H94 in patients with anemia cancer and ESA hyporesponsive anemia dialysis
were performed [169]. Treatment with NOX-H94 causes an increase in hemoglobin
(Hb) levels, suggesting that inhibition of hepcidin may also be an effective target for
the treatment of cancer-related anemia with functional iron deficiency.
6.4.4.2 TGF-β
There are three subtypes of TGF-β, among which TGF-β1 is the most common
subtype in various tissues. As a pro-inflammatory cytokine, TGF-β1 induces chemotaxis by stimulating the migration of monocytes, lymphocytes, neutrophils, and
fibroblasts [170]. In addition, TGF-β1 and IL-4 together induce T cell differentiation
and produce IL-9 and IL-10 to implement inflammatory function [171]. Recently,
results of an in vitro study indicating that TGF-β1 inhibited the activation of primitive
CD8+T cells and the secretion of interferon gamma (IFN-γ), meanwhile, increased
the survival and memory CD8+T cells and the synthesis of IL-17 and IFN-γ [172].
In addition, TGF-β induces pro-inflammatory or anti-inflammatory responses in a
dose-dependent manner. Kang et al. [173] obtained an anti-TGF-β1 phosphorothioate
DNA aptamer. By phosphorylating the 5
of adenosine and cytosine in the ssDNA
backbone (K D = ∼90 nm), the affinity and nuclease resistance of the aptamers
improved significantly.
6.5 Aptamers for Targeted Therapy of Cancer
Aptamers participate in cancer-related targeted therapy as agonists or inhibitors.
Aptamer agonists co-stimulate the receptor–ligand interaction of the target, induce
effective signal pathways on the surface of antigen-presenting cells or T cells, and
optimize cancer immunotherapy. Aptamer inhibitors realize the loss of target function
by inhibiting the activity of the target or blocking the interaction between the target
and its receptor/ligand (Fig. 6.6). This part introduced the development of typical
aptamer agonists and blockers in cancer therapy.
G. Yang and Y. Huang
6.4.4 Other Inflammatory-Associated Factors
6.4.4.1 Hepcidin
A 44 nt L-type RNA aptamer NOX-H94 binds to human iron metabolism regulator
hepcidin, thereby preventing hepcidin-induced iron port protein degradation and
ferritin expression [168]. Inhibiting hepcidin is an efficient path of chronic inflammatory anemia therapy. In a pharmacodynamic study of healthy individuals, NOX-H94
blocked the effect of hepcidin on serum iron levels. Recently, two phase 2 evaluations
of NOX-H94 in patients with anemia cancer and ESA hyporesponsive anemia dialysis
were performed [169]. Treatment with NOX-H94 causes an increase in hemoglobin
(Hb) levels, suggesting that inhibition of hepcidin may also be an effective target for
the treatment of cancer-related anemia with functional iron deficiency.
6.4.4.2 TGF-β
There are three subtypes of TGF-β, among which TGF-β1 is the most common
subtype in various tissues. As a pro-inflammatory cytokine, TGF-β1 induces chemotaxis by stimulating the migration of monocytes, lymphocytes, neutrophils, and
fibroblasts [170]. In addition, TGF-β1 and IL-4 together induce T cell differentiation
and produce IL-9 and IL-10 to implement inflammatory function [171]. Recently,
results of an in vitro study indicating that TGF-β1 inhibited the activation of primitive
CD8+T cells and the secretion of interferon gamma (IFN-γ), meanwhile, increased
the survival and memory CD8+T cells and the synthesis of IL-17 and IFN-γ [172].
In addition, TGF-β induces pro-inflammatory or anti-inflammatory responses in a
dose-dependent manner. Kang et al. [173] obtained an anti-TGF-β1 phosphorothioate
DNA aptamer. By phosphorylating the 5
of adenosine and cytosine in the ssDNA
backbone (K D = ∼90 nm), the affinity and nuclease resistance of the aptamers
improved significantly.
6.5 Aptamers for Targeted Therapy of Cancer
Aptamers participate in cancer-related targeted therapy as agonists or inhibitors.
Aptamer agonists co-stimulate the receptor–ligand interaction of the target, induce
effective signal pathways on the surface of antigen-presenting cells or T cells, and
optimize cancer immunotherapy. Aptamer inhibitors realize the loss of target function
by inhibiting the activity of the target or blocking the interaction between the target
and its receptor/ligand (Fig. 6.6). This part introduced the development of typical
aptamer agonists and blockers in cancer therapy.