Co-ordinating immunity against cancer
The growing knowledge from human cancer studies suggests a central role for myeloid cells that warrants their consideration in future diagnostic and therapeutic approaches . Myeloid cells known as M1 macrophages and dendritic cells (DCs) can induce both innate and adaptive effector cells to drive tumour rejection .
PG545 (pixatimod, pINN) is a novel immunomodulatory agent which has been demonstrated to affect the functions of myeloid cells leading to anti-tumour responses in mouse models.
First, it stimulates DC via TLR9/IL-12 to activate natural killer (NK) cells capable of destroying lymphomas in vivo .
Second, it blocks tumour-associated macrophages (TAMs) in mouse models, which has been associated with the inhibition of heparanase [4,5]. PG545 recently completed a phase Ia clinical trial as a monotherapy in solid tumours showing that it was safely tolerated to 100 mg, weekly (ClinicalTrials.gov Identifier: NCT02042781).
1 Engblom C et al. (2016) Nat Rev Cancer. 16: 447-62.
2 Mills CD et al. (2016) Cancer Res. 76: 513-6.
3 Brennan TV et al. (2016) J Clin Invest. 126: 207-19.
4 Ostapoff KT et al. (2013) Mol Cancer Ther. 12: 1190-201.
5 Boyango I et al. (2014) Cancer Res. 74: 4504-14.