Gentuzumab ozogamicin, a drug used to treat acute myeloid leukaemia, may also hold the key to making immunotherapy successful for solid tumour cancers, British researchers have reported.
Myeloid-derived suppressor cells (MDSCs) are immune cells present in the tumours and blood of cancer patients. The protective environment that MDSCs create is thought to be the reason why CAR-T cell therapy in solid cancers has not been as successful as has been hoped. Scientists hope that killing or inactivating these cells would help to improve immunotherapy for cancer patients.
In this latest study, a team at the University of Birmingham isolated MDSCs from blood samples from 200 newly-diagnosed cancer patients, both adults and children. They discovered that MDSCs send out a “barrage” of signals to protect tumours from killer T cells.
The team found that these MDSCs produced the protein CD33, the target of the antibody drug gentuzumab ozogamicin, also known as Mylotarg. Lab experiments showed that gentuzumab ozogamicin killed MDSCs, increasing T cell proliferation and the effectiveness of CAR‑T cell therapy against some solid tumours.
The researchers say this suggests a way to make CAR-T therapy and other immunotherapies more effective for solid tumours. The findings were published in the online journal EBioMedicine last week.
The findings also suggest that gentuzumab ozogamicin could be used to treat hemophagocytic lymphohistiocytosis and macrophage activation syndrome, rare diseases caused by overreaction to infections and other triggers. This approach is now being tested in a phase II clinical trial, which is also open to patients with solid tumours.
Dr Francis Mussai, who co-led the study with Dr Carmela De Santo, said: “This is the first time we’ve been able to effectively target the immune cells that form a barrier around solid tumours.
“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 from Cancer Research UK, which part-funded the study, 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.”
Source: Fultang, L., Panetti, S., Ng, M., Collins, P., Graef, S., Rizkalla, N., Booth, S., Lenton, R., Noyvert, B., Shannon-Lowe, C., Middleton, G., Mussai, F., De Santo, C. (2019) “MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers”, EBioMedicine, available from doi: 10.1016/j.ebiom.2019.08.025
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