Synergistic Pathways Offers Animal Models Protection From Cancer
PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DCs).
DC signals can be bypassed by CD27 agonists and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).
Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models, by researchers at the University of Southampton. When given alone, each treatment produced 10% protection from cancer, but when administered together, they provided 60% protection, they have now reported.
Professor Aymen Al-Shamkhani, who heads the laboratory in which the study was carried out, said: “Using checkpoint blockade has revolutionised the field of cancer immunotherapy, but it is not enough to simply stop the cancer from evading the immune system, we need to boost the immune system to fight the cancer off. By combining checkpoint blockade with an anti-CD27 antibody, we have been able to show that the two approaches can be harnessed to potentially improve current treatment options.”
The study, funded by Celldex
Therapeutics and Cancer Research UK, also revealed that the combination treatment activated different, yet synergistic pathways that culminated in stronger immune responses against the cancer. The research team say this pre-clinical work supports on-going clinical trials that are already testing the combination in patients.Dr Catherine Pickworth, from Cancer Research UK, said: “Immunotherapy treatments are already showing huge promise for a number of cancer types, but they don’t work for everyone. This work in mice suggests that using two types of immunotherapy could be an effective way to tackle this problem. Now we need to see if this particular approach works in patients. Cancer Research UK is funding several studies, looking at combining different types of immunotherapy so we can provide more treatment options and help more people beat their cancer.”
