Cancer's protective barrier could be removed
Scientists from the University of Birmingham have utilised an existing antibody drug to pull down the protective wall that surrounds tumours, potentially re-exposing them to the killing power of the immune system and immunotherapy treatments. Their work has been published in the journal EBioMedicine.
The research was led by Drs Francis Mussai and Carmela De Santo, who were studying immune cells called myeloid-derived suppressor cells (MDSCs) taken from the blood of 200 adults and children newly diagnosed with cancer. These cells send out a barrage of chemical signals that shield tumours cells from the immune system and the effects of treatment, and prevent the activation of T cells that can kill tumour cells. When MDSCs are present in higher numbers the outlook for patients is worse, as their cancer can become resistant to treatment and is more likely to spread to other parts of the body.
“Treatments that work with the immune system to kill cancer often fail because it can be difficult for our body’s defences to get access to the tumour cells,” Dr Mussai said.
Previously, researchers in another group found a way to break the protective layer around tumours in mice by using antibodies that attach to the MDSC cell surface, marking it for destruction by the immune system. But translating this into clinical trials has been challenging because researchers have been unable to find a drug target that is present on human MDSCs.
Analysis of their 200 blood samples revealed to the Birmingham researchers that a protein called CD33 is present on the surface of MDSCs across a wide range of cancers. By using an antibody drug called gentuzumab ozogamicin that targets CD33, which is already used to treat acute myeloid leukaemia, the researchers were able to kill the MDSCs in the samples and restore the ability of T cells to attack the tumour cells.
The researchers also showed that active MDSCs prevent CAR-T cells from working — these are T cells that have been reprogrammed in the lab to make them more effective at killing cancer cells. But when they added the antibody drug, it boosted the activity of the CAR-T cells.
“Our research indicates that giving this antibody drug alongside immunotherapies could dramatically increase the number of patients benefiting from the latest innovations in treatment,” Dr Mussai said.
“This is the first time we’ve been able to effectively target the immune cells that form a barrier around solid tumours,” added Dr Mussai. “If this approach works in patients it could improve treatments for many different types of cancer, in both adults and children. We envision our approach will have the most impact in CAR-T therapy, which, despite showing lots of promise in blood cancer, so far it’s had limited success in solid tumours.”
In addition to treating a range of cancers, the findings could also be applicable to treating HLH (hemophagocytic lymphohistiocytosis) and MAS (macrophage activation syndrome), where the body reacts inappropriately to triggers such as infections. These disorders are extremely rare and as a result there are few treatments available, particularly to children with HLH.
The team are now planning a clinical trial to test the safety and activity of the antibody drug in people with HLH and MAS. The trial will also include people with solid tumours.
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