Anti-cancer Therapy May Help Fight Inflammation in SSc Patients, Data Suggest

Anti-cancer Therapy May Help Fight Inflammation in SSc Patients, Data Suggest
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Tagraxofusp

Tagraxofusp, a medicine approved in the U.S. under the name Elzonris to treat a rare blood cancer, may help decrease levels of immune cells that promote inflammation in systemic sclerosis (SSc), new preclinical data suggest.

The results were shared in a poster, “CD123+ plasmacytoid dendritic cells (pDCs) from systemic sclerosis patients are susceptible to the cytotoxic activity of tagraxofusp, a CD123-targeted therapy,” at the 2019 European Congress of Rheumatology (EULAR) in Madrid.

Tagraxofusp, also known as SL-401, is an engineered antibody developed by Stemline Therapeutics to target a protein called CD123, or IL-3 receptor (IL-3R).

It results from the combination of the interleukin (IL)-3 molecule with a diphtheria toxin. This makes tagraxofusp able to specifically target cells that are positive for CD123; once the antibody is inside, the cells die because of the toxin.

The antibody was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children age 2 or older. This rare type of blood cancer derives from precursor cells of a subtype of immune cells, called plasmacytoid dendritic cells, which are positive for CD123.

Plasmacytoid dendritic cells are known for secreting interferon-alpha (IFN-alpha), a signaling molecule that plays an important role in inflammation and progression of diseases, such as SSc and lupus.

Researchers at Stemline Therapeutics believe that by depleting or attenuating the activity of these immune cells, it could be possible to achieve therapeutic benefits for SSc patients.

To further explore the potential of tagraxofusp, researchers isolated immune cells from blood samples of five SSc patients and five healthy donors and exposed them to the antibody.

Tagraxofusp was able to specifically induce the death of both healthy and SSc plasmacytoid dendritic cells, with low toxicity to other immune cell populations, such as B cells or T cells. The treatment also reduced the release of IFN-alfa by 68-fold in SSc cells, along with a 3-fold decrease in a gene activated by IFN-alfa.

These therapeutic benefits were achieved using a dose of tagraxofusp lower than that used in the clinic in children with BPDCN.

Overall, these results suggest that tagraxofusp might be a potential therapeutic approach for SSc or other autoimmune diseases.

Stemline Therapeutics is planning a clinical trial to test the safety and potential of Elzonris in patients with autoimmune diseases.

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