An investigational drug that boosts the response of natural killer (NK) cells — key players of first-line immune defenses — was recently shown to effectively decrease ovarian tumors in a mouse model of the cancer. The drug, called ALT-803, could also re-activate inactive NK cells isolated from ovarian cancer patients.
Researchers now plan to study the drug candidate in a clinical trial (NCT03054909) to see if ALT-803 can prevent women with ovarian cancer, who have undergone successful chemotherapy, from relapsing. The drug is a particularly attractive treatment option since it can be administered on an outpatient basis.
The study, “IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer,” was published in the journal Gynecologic Oncology.
NK cells are being explored as a new tool for cancer immunotherapy. Earlier studies have shown that cells isolated from healthy donors attack ovarian tumors, both in lab dishes and in patients. Studies also confirm that NK cells, isolated from the fluid in the abdomen of ovarian cancer patients, react poorly to the presence of tumors.
Aiming to find a way to re-activate these cancer-fighting cells, researchers from the University of Minnesota tested ALT-803 — developed by Altor BioScience — that has been developed to stimulate signaling by the immune cytokine interleukin 15 (IL-15). This immune mediator is known to trigger NK cell responses to tumors.
Using lab-grown NK cells from both healthy volunteers and ovarian cancer patients, researchers showed that ALT-803 made the cells multiply. Experiments showed that the treatment triggered the production of other cytokines in patient-derived cells, which also regained their former appearance and ability to target tumors.
Researchers next tested whether the drug would have the same beneficial effects in a living organism. They used mice, which grew human ovarian tumors, and injected the drug into their abdomen or under the skin. The tumors were genetically engineered to emit light, allowing researchers to visualize them.
While the injection of human NK cells alone reduced tumor volumes, the largest reductions were seen in mice that also received ALT-803. Analyses also confirmed that the cells multiplied more inside the mice after drug treatment, just as researchers had observed in the lab dishes.
ALT-803 is already in clinical trials for other cancer forms, and the research team is now planning to study whether a maintenance treatment with the drug can prevent women with ovarian cancer from relapsing.