Table 1.
Synergistic effects of oligodeoxynucleotides combined with synthetic compounds on immunotherapy.
| Synergistic compounds | Activated immune response | Stimulated cells | Regulation of cytokine expression | Immunotherapy | References |
|---|---|---|---|---|---|
| CpG-ODN +GMCSF | Enhanced Th1 response | CD80 and CD86 stimulation | Induced IL-6 and IL-12 | Evaluation in tumor immunization | (112) |
| CpG-ODN +IL-15 | Significant rise in iCa+ followed by rapid apoptosis | CD38+ progeny | IL-2, IL-10 | Treatment of B-CLL | (113) |
| CpG-ODN +STING ligand | Th1 response and suppressed Th2 | Induced CD8+ T cells | IFN-γ, IL-12 | Promising antitumor agent | (114) |
| CpG-ODN +TLR2 neutralizing antibody | Enhanced infiltration of NK cells and CTLs. Reduced type-2 macrophages and Tregs | Production of CD8/CD4 | Suppression of TGF-β1, cyclooxygenase-2, and indoleamine 2,3-dioxygenase | Immunotherapeutic against Lewis lung carcinoma | (95) |
| CpG-ODN (1826) +IL-10 siRNA | Enhanced Th1 response, also induced Th2 | CD86, CD80, and CD40 were expressed at a significantly higher percentage on BMDCs | Upregulated IL-12 p35 and IL-12 p40 in BMDCs | DNA vaccine in a mouse model of B-cell lymphoma | (116) |
| CpG-ODN (2216) +poly I:C (TLR3 ligand) | Enhanced Th1 response | Induced B-cell response | Induced type I-IFN, IL-6, and IL-10 | Use as vaccine Potential immunoregulatory function controlling unwanted inflammation | (57, 118) |
| CpG-ODN +poly I:C (TLR3 ligand) +antigen | Maturation of mAPCs in human immune cells | CD80 and CD86 stimulation | Induced IL-6, type I/II-IFN, IL-12, and TNF-α | Cancer prevention vaccine | (117) |
| CpG-ODN +γ-PGA-Phe (TLR4 stimulator) | Synergistically activated macrophages and induced Th1 response | Antigen-specific IFN-γ-producing T cells | Induced TNF-α | Vaccine delivery and adjuvant system | (119) |
| CpG-A +imiquimod (TLR7 ligand) | Promoted memory cell activation linked to DC activation | Induced effector CD8+ T-cell responses | Upregulation of IFN-α | T-cell vaccination against infections and malignant diseases | (120, 121) |
| CpG-ODN (1826) +gardiquimod (TLR7 ligand) | Induced macrophage tolerance | Negative regulation of SOCS1 | Reduced TNF-α and IL-6 expression | Impaired response in chronic viral infection | (115) |
| CpG-ODN (MsST) +iSN34 | Enhanced Th1 response | Production of CD19+IL-6+ cells | Induced IL-6 expression | Prevention or treatment of dysfunction of innate and adaptive immunity | (47) |
| iSN34 +Pam3CSK4 (TLR1/2 ligand), LPS (TLR4 ligand), and zymosan (TLR2/6) ligands | Enhanced Th1 response | Production of CD19+IL-6+ cells | Induced IL-6 expression | Use as agonists and novel therapeutics for inflammatory diseases driven by TLR-mediated immune activation | (48) |
This table lists representative examples of the synergistic activity of ODNs with other molecules and the immunomodulatory activity of the abovementioned immunosynergistic effects.
GMCSF, granulocyte macrophage colony-stimulating factor; B-CLL, B-cell chronic lymphocytic leukemia; TGF, transforming growth factor; CTL, cytotoxic T lymphocyte; Treg, regulatory T cell; STING, stimulator of interferon genes; LPS, lipopolysaccharide; poly (I:C), polyinosinic-polycytidylic acid; DC, dendritic cell; IFN, interferon; SOCS1, suppressor of cytokine signaling 1; TNF, tumor necrosis factor; Pam3CSK4, synthetic triacylated lipopeptide; Th1, T helper type 1.