Chordoma Foundation

New findings suggest a role for natural killer cell based therapies against chordoma

Natural killer cell. Photo: National Institutes of Allergy and Infectious Diseases, National Institutes of Health

Immunotherapy, an approach that harnesses the immune system to treat disease, has shown impressive results against a number of cancers. Now, new preclinical findings from research that the Chordoma Foundation helped to initiate and fund have opened the door to expanding the immunotherapy toolbox for chordoma. While much immunotherapy research focuses on T cells, this study demonstrates that natural killer (NK) cells — another important arm of the immune system — could also be leveraged to fight chordoma, and suggests that a combination of immunotherapies can enhance the ability of NK cells to attack chordoma cells.

The new paper was published in Cancer Research Communications by cancer immunotherapy experts Nyall London, MD, PhD of Johns Hopkins University School of Medicine and the National Institutes of Health (NIH), James Hodge, PhD of the NIH, and their teams. The scientists evaluated various therapeutic combinations of an anti-PD-L1 antibody, an anti-EGFR antibody, and an immune-stimulatory drug on NK cells’ ability to galvanize against six different chordoma cell lines.

The anti-PD-L1 antibody used in this study was similar to a drug called avelumab, which has shown preclinical efficacy against chordoma in previous work by Dr. Hodge’s team. It belongs to a class of drugs called immune checkpoint inhibitors, which have produced sustained disease control against a number of cancers. The anti-EGFR antibody in this study was cetuximab; EGFR is one of the most well-validated therapeutic targets in chordoma.

Drs. London and Hodge and colleagues found that each of the therapies worked to promote chordoma cell killing by NK cells and, importantly, combination treatment synergistically enhanced this effect. They also found evidence that these approaches might be able to selectively target chordoma cancer stem cells, a subtype of tumor cells that are thought to promote cancer formation and recurrence.

Taken together, these findings contribute to our understanding of how the immune system can be leveraged to treat chordoma, and could serve as the basis for a future clinical trial. They also lend further support and rationale to the new cetuximab clinical trial, which will open very soon for chordoma patients.

Through our Immunotherapy Initiative, we’re investing in research to ensure chordoma patients benefit from extraordinary advances being made in this field. Among our most recent investments is a grant to Dr. London and colleagues for a project to characterize the way chordoma tumors interact with the immune system, with the goal of generating new ideas about how to treat chordoma.


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