A study conducted by the Johns Hopkins Kimmel Cancer Center revealed a new treatment that helped shrink prostate and bladder cancer in mice by “programming immune cells to enhance anti-tumor activity.”
The study's lead author, Jilani Zarif, explains that immune cells called "macrophages" may, in some circumstances, be responsible for stimulating tumors to grow and inhibiting the activity of T cells, which hinders the immune response to cancer.
“The focus of our work is to reprogram macrophages into anti-cancer immune cells to enhance responses to immunotherapies and other standard cancer treatments,” says Zarif.
Immunosuppressive macrophages depend on the amino acid glutamine. The research team has previously demonstrated that primary macrophages, called monocytes, will develop into immune-stimulating macrophages if they are grown in a laboratory environment without glutamine. When monocytes are cultured with glutamine, they become immunosuppressive macrophages.
The researchers hypothesized that drugs that prevent immune cells from accessing glutamine could shift macrophages toward the immune-stimulating type and help shrink tumors.
Zarif used an experimental drug to block glutamine, developed by a number of study participants, called JHU083, which is a type of molecule called a “prodrug” that cells inside the body convert into an “active drug.”
Studies have revealed that the drug shrinks tumors, reduces the spread of cancer, and increases the chances of survival in animals with skin, colon, blood, and brain cancer, in addition to some types of breast cancer that are resistant to treatment.
Zarif explains: “The research team changed the chemistry of the drug so that it could spread inactively throughout the body, and only become active when it enters cancer cells.”
The team showed that JHU083 inhibits glutamine utilization in prostate and bladder tumors in mice, reducing tumor growth and leading to cancer cell death. He also reprogrammed macrophages to stimulate them to destroy cancer cells.
“JHU083 could be a promising anti-cancer treatment, especially in tumors that contain immunosuppressive macrophages and very few T cells,” Zarif says.
The team plans to collaborate with researchers at Johns Hopkins University to launch a clinical trial of the drug JHU083 that includes patients with treatment-resistant prostate or bladder cancer.
The study was published online in the journal Cancer Immunology Research.