The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

Table 1

Immunotherapies with a demonstrated local antitumour effect.

Agent	Mechanism	Reference
IL-2/anti-CD40 mAb	Licensing of local and systemic CTL	[24, 25, 29, 40, 91]
Anti-CD40 mAb	Licensing of CTL by dendritic cells but can also promote angiogenesis	[24, 27, 88–91]
Anti-CTLA-4 mAb	Immunes checkpoint blockade, enhances Teff response by blocking CTLA-4 inhibitory signals, and limits Treg function	[62–66]
Anti-PD-1 mAb	Blocks PD-1 mediated T cell inhibition, particularly when used in conjunction with anti-CTLA4 therapy	[68–73]
p300	Targeted inhibition of p300 impairs Treg function	[56]
TLR7 agonist	Activates DCs	[92]
TLR 3/9 agonists	TLR mediated, Type I IFN dependent activation of preexisting intratumoural CD8 T cells	[94, 95]
Viral-cytokine constructs	Infection of different cell types in tumour microenvironment, persistent cytokine expression and increased antigen cross-presentation	[111, 113, 121–124]
Cytokine or alloMHC transfection	IL-2, IL-12, GMCSF, and B7.1 enhance antitumour immunity	[116–120, 125]
Cyclophosphamide	Potentiation of antitumour immunity by targeting of Treg	[58–60]
Chemotherapy	Direct tumour cytotoxicity	[99–110]