Cancer Immunotherapy: Inducing Dendritic Cell Maturation

Mature dendritic cells (DC) upregulate antigen presentation and co-stimulatory molecules on their surface as well as the production of inflammatory cytokines. This process can be induced by triggering receptors with cytokines, small molecules, or damage associated molecular patterns (DAMPs). It can be modulated by blocking the activity of molecules that normally inhibit DC maturation. Targeting uptake receptors that enable antigen cross-presentation can increase the ability of DC-based vaccines to trigger NK and CD8+ T cell cytolytic activity directed at the tumor cells.

 

pDC Maturation Inducers pDC Maturation Inhibitors
 
mDC Maturaton Inducers mDC Maturation Inhibitors

 

pDC Inducers
Adenosine A1 R Agonists GM-CSF IL-10 TLR2 agonists
Adenosine A2a R agonists GRP78/HSPA5 MFG-E8 TLR4 agonists
Adenosine A2b R Agonists Histones P2X R Agonists TLR7 agonists
Adenosine A3 R Agonists HSP60 P2Y R Agonists TLR9
Non-selective Adenosine R Agonists  HSP70/HSPA1A Phosphatidylserine Toll-like Receptor Agonists
CD24 HSP90 RAGE  
CD40 Ligand/TNFSF5 HMGB1/HMG-1 Synuclein-alpha  
CD40 Agonistic Antibodies IL-3 TIM-3 Agonistic Antibodies  
pDC Maturation Inhibitors
A20/TNFAIP3 DEC-205/CD205 Fc epsilon RI alpha Siglec-H
DCIR/CLEC4A DLEC/CLEC4C/BDCA-2 NKp44 Agonistic Antibodies Wnt5a
mDC Maturaton Inducers
Bombesin Receptor Antagonist IL-1 beta/IL-1F2 TLR4 agonists
CD40 Ligand/TNFSF5 IL-6 TLR7 Agonists
CD40 Agonistic Antibodies IL-10 R alpha Blocking Antibodies Toll-like Receptor Agonists
DC-SIGN/CD209 IL-10 R beta Blocking Antibodies TNF-alpha
Dectin-1/CLEC7A IL-12 VEGF R1 Blocking Antibodies
GM-CSF Neuromedin B Receptor Antagonists VEGF R2 Blocking Antibodies
IFN-alpha Prostaglandin E2/PGE2  
IFN-gamma TLR3 Agonists  
mDC Maturation Inhibitors
A20/TNFAIP3 IL-10 Vitamin D Receptor Agonists
Bombesin M-CSF Additional Vitamin D Receptor Compounds
Bombesin Receptor Agonists VEGF  
GDF-15 VitD3  

CTLA-4 Blocking Antibodies
4-1BB/TNFRSF9