Antibody activating an immune cell protein may treat COPD

VSTM-1 protein lowers the inflammatory activity of cells like neutrophils

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Scientists at NextCure have developed a monoclonal antibody targeting the protein VSTM-1, which the company hopes to develop as a treatment for inflammatory lung disorders such as chronic obstructive pulmonary disease (COPD).

“We believe we have a real opportunity to change the standard of care in COPD, and other chronic inflammatory diseases, and address a key unmet need,” Solomon Langermann, PhD, chief scientific officer of NextCure, said in a company press release.

Langermann joined other NextCure scientists in presenting findings from tests of the antibody at the Keystone Symposium for Inhibitory Receptors in Immune Homeostasis, Disease and Therapy. Work was detailed in the poster, “VSTM-1 Agonist mAb Therapy Reduces Granulocytic Inflammation And COPD.”

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Research into treating COPD via the VSTM-1 protein on immune cells

The VSTM-1 protein is expressed on the surface of certain immune cells, including neutrophils and monocytes. When VSTM-1 is activated, it reduces the inflammatory activity of these cells, which normally helps to regulate their activity.

In inflammatory lung diseases like COPD where these immune cells are overactive, activating VSTM-1 might be a useful therapeutic strategy.

The company’s monoclonal antibody —  a lab-made antibody with high specificity — was able to bind to and activate the VSTM-1 protein.

In early experiments in cells, the researchers showed that their VSTM-1 stimulating monoclonal antibody appeared to lower inflammatory activity as designed. For example, neutrophils treated with the antibody produced significantly lower levels of pro-inflammatory signaling molecules.

To test the antibody in an animal model, the scientists engineered mice to express the human version of the VSTM-1 protein in their neutrophils. Then, to induce COPD-like lung inflammation, a bacterial molecule was administered into the mice’s lungs.

Findings from this animal model, consistent with the initial cell experiments, demonstrated a significant reduction in inflammatory activity in mice treated with the monoclonal antibody.

“These preclinical data support targeting of VSTM-1 as a novel therapeutic intervention for chronic inflammatory diseases of the lung,” the scientists wrote.

“The VSTM-1 [activating monoclonal antibody] that we are advancing preclinically provides a differentiated approach with a unique mechanism to ameliorate pulmonary inflammation and the potential to treat and prevent chronic lung disease, including COPD,” Langermann said.

Researchers now are working to optimize this antibody for use as a therapy, aiming to get maximum efficacy with minimal off-target effects. They also plan to test the antibody in combination with existing disease treatments.