Researchers from the Johns Hopkins Kimmel Cancer Center and Johns Hopkins Drug Discovery have revealed that a novel therapy can reprogramme immune cells to shrink hard-to-treat prostate and bladder cancers.
Published in the journal Cancer Immunology Research, researchers found that the drug, JHU083, reduced tumour growth and triggered tumour cell death in mice.
Currently the third-most common cancer in the US, prostate cancer occurs when cells grow uncontrollably within the prostate gland, while bladder cancer is characterised by abnormal cells which grow in the bladder lining or muscle.
Researchers aimed to reprogramme the immune-suppressive tumour-associated macrophages into anticancer immune cells to “enhance therapeutic responses to immunotherapies and other standard-of-care cancer therapies,” explained Jelani Zarif, Robert E Meyerhoff endowed professor and associate professor, oncology, Johns Hopkins.
Macrophages help tumours to grow and suppress t-cell activity and inhibit an immune response to cancers. They use monocytes, macrophage precursor cells, to develop into immune-activating macrophages when grown without glutamine, an amino acid.
JHU083 is a type of molecule known as a prodrug that enables cells inside the body to convert into an active glutamine-blocking drug from inside the tumour.
In mice, researchers showed that JHU083 blocks the use of glutamine in prostate and bladder tumours, reducing tumour growth and triggering tumour cell death, while also reprogramming immune-suppressing macrophages into immune-boosting macrophages.
In doing so, the macrophages started destroying tumour cells and also helped to recruit tumour-killing T-cells and natural killer cells to the tumours.
“JHU083 could be a promising anti-cancer therapy for tumours with immune-suppressing macrophages and too few T-cells,” and “might also be a promising agent for tumours that do not respond to checkpoint inhibitors,” explained Zarif.
Researchers plan to launch a clinical trial for JHU083 in patients with treatment-resistant prostate or bladder cancer to determine whether it shrinks tumours and prevents metastasis, while also continuing studies on whether combining the drug with other treatments could improve its effectiveness against tumours.
