A National Cancer Center (NCC) research team said it has developed a new therapeutic agent that can greatly improve the therapeutic effect and solve immune checkpoint inhibitor problems used in existing immunotherapies.

Cancer cells overexpress an immune checkpoint protein called PD-L1 (programmed death-ligand 1) on the cell surface, which interacts with toxic T-cells and makes normal T-cells unable to attack cancer cells even if they recognize them.

As a result, global pharmaceutical companies are focusing on developing antibody-based immune checkpoint inhibitors that inhibit the interaction between the PD-L1 immune checkpoint protein in cancer cells and toxic T-cells.

However, immune checkpoint inhibitors made from existing antibodies are economically burdensome for cancer patients due to high costs, and the therapeutic effect is insignificant when cancer cells are rapidly proliferating, or the tumor size is large.

Also, with the recent increase in the use of immune checkpoint inhibitors, hospitals are witnessing serious side effects such as cardiotoxicity.

To resolve this issue, the team, led by Doctor Goh Sung-ho and Choi Yong-doo, confirmed through an animal experiment that when FOXM1 inhibitors are treated on cancer cells, it prevents the cancer cells from making PD-L1 proteins, inhibit the proliferation of cancer cells, and induce the death of cancer cells to effectively treat cancer.

Notably, when the FOXM1 inhibitor and the immune checkpoint inhibitor were administered simultaneously in a lung cancer animal model showing immunotherapy resistance, the immunotherapeutic effect was significantly improved compared to when each was administered alone.

Also, since the FOXM1 inhibitor only acts on the highly expressed FOXM1 protein in cancer cells, the team found that the FOXM1 inhibitor did not cause side effects on normal tissues when treated alone or in combination with an immune checkpoint inhibitor.

"Since FOXM1 protein is overexpressed in several carcinomas such as lung cancer and colorectal cancer, we expect that immunotherapy using FOXM1 inhibitors will become an alternative that can dramatically improve the efficacy of immunotherapies in various carcinomas without side effects," Professor Goh said.

Professor Choi also said, "FOXM1 inhibitors have a low production cost, which will significantly reduce the patient's medical cost burden and effectively provide treatment to a large number of patients."

The team expects that the clinical effect will be verified in the future and applied to actual cancer treatment, Choi added.

Advanced Science published the result of the study.