Agent | Rationale for combining with radiotherapy | References |
---|---|---|
CTLA-4 Inhibitor | Immune checkpoint inhibitor. Combination with RT has induced responses in patients where anti-CTLA4 alone had failed. Systemic responses have been observed in patients receiving RT + anti-CTLA4 | |
PD-1/PD-L1 Inhibitor | Immune checkpoint inhibitor. Systemic responses have been observed when combined with RT. Increased progression free survival and overall survival observed in patients with NSCLC who received RT + anti-PD1 | |
CD40 Agonist | Enhances DC function, stimulates T-cell trafficking, and activates M1 polarized macrophages, so may overcome immunosuppression. Successful anti-tumour immune responses observed in mice receiving RT + CD40 | |
TLR Agonist | Activates T-cells, blocks immunosuppressive effects of MDSCs and tumour associated macrophages. May convert MDSC into immunostimulatory antigen presenting cells | |
CCL2/5 Inhibitor | Prevents monocyte recruitment to the tumour microenvironment and improves responses to RT in pre-clinical studies | |
Mer-TK Inhibitor | Inhibits tumour associated macrophages. Tumour regression observed when combined with RT. Induced responses in ‘cold’ tumours with the addition of RT and a TGFβ inhibitor. Delayed metastasis and improved survival when combined with anti-PD1 and RT in pre-clinical studies | |
PARP Inhibitor | Inhibits tumour damage response pathways. Increases T-cell infiltration and increases PD-L1 expression, so could be combined with anti-PD1 and RT | |
TGFβ Inhibitor | Inhibits immunosuppressive effects of TGFβ. Enhances T-cell infiltration in combination with anti-PD1. Combination with RT and anti-PD1 induced greater responses compared to anti-PD1 alone | |
PDE5 Inhibitor | Increases T cell infiltration and activation by reducing MDSC function. Improved outcomes observed in patients with metastatic melanoma |