A study, part funded by Cancer Research UK, has investigated removing the protective wall that surrounds tumours as a potential strategy to boost the success of immunotherapy treatments.
Scientists studied myeloid-derived suppressor cells (MDSCs) taken from the blood of adults and children newly diagnosed with cancer prior to initiation of treatment.
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.
Dr Francis Mussai, lead author of the study and Cancer Research UK Clinical Scientist Fellow at the University of Birmingham, said: “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. Our research indicates that giving this antibody drug alongside immunotherapies could dramatically increase the number of patients benefitting from the latest innovations in treatment.”
Previously, researchers in another group had 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’s present on human MDSCs.
In this latest study, the team used blood samples taken from patients and showed that a protein called CD33 is present on the surface of MDSCs across a wide range of cancers.
By using the 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 prevented CAR-T cells from working. But when they added the antibody drug, it boosted the activity of the CAR-T cells.
“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.”
Dr Emily Farthing, research information manager at Cancer Research UK said: “Although this is early research, it’s increased our understanding of the way tumours interact with the immune system, and has given us a tantalising insight into how we could make immunotherapies work for more patients in the future. But we are still a long way off in getting this treatment to patients. The next step will be to learn more about the side effects of the antibody drug, and how it works in the body.”
In addition to treating a range of cancers, the findings could also be applicable to treating HLH (haemophagocytic lymphohistiocytosis) and 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.
