Mark Schroeder, MD, Discusses Treatment Options for Acute GvHD

Mark Schroeder, MD, discussed JAK inhibitors, alpha 1 antitrypsin and IL-22 receptors as potential treatment options for acute graft versus host disease (GvHD).

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I focused on 3 specific treatments for acute graft versus host disease: JAK inhibitors, alpha 1 antitrypsin and then a novel agonist antibody called IL-22.

So, JAK inhibitor therapy works by blocking cytokines, which are essential for stimulating the GvHD response. In fact, JAK stat signaling is critical for immune cell development, and by blocking this with JAK inhibitors such as ruxolitinib, which is a JAK 2 inhibitor, or itacitinib, a JAK 1 inhibitor, you can block these essential signals which are critical for proliferation of T-cells or development of T-cell subsets that lead to suppression such as regulatory T-cells.

The other aspect that we spoke about in the talk was alpha 1 antitrypsin. It works a little bit different than JAK inhibition, it works more upstream in decreasing the inflammatory milieu in the gut. It’s a searing protease inhibitor-protease is produced by cells like neutrophils which leads to chronic inflammation, and by doing that, inflammatory cytokines are reduced. And when you reduce inflammatory cytokines, you can alter the number and types of cells that are present within say the gut or target organs of GvHD.

The third therapy we talked about is an IL-22 agonist, which is being presented at the TCT meeting. This drug is a novel homodimer of IL-22 that’s conjugated to an immunoglobulin and it acts to stimulate the IL-22 receptor. The IL-22 receptor is on epithelial cells that line organs like the gut or the lung, and by stimulating IL-22, which is on intestinal stem cells, you can promote intestinal regeneration.