Zaxia: Novel Photosensitizer Prevents Graft-Versus-Host Disease
Zaxia, a novel photosensitizer that uses highly selective photodepletion to prevent graft-versus-host disease in patients receiving hematopoietic stem cell transplantation.
Researchers at Wake Forest Baptist Medical Center have developed a highly selective technology to target and eliminate GVHD-causing T-cells prior to transplant using a proprietary photosensitizer named Zaxia. This novel technology eliminates pathogenic T-cells while actively protecting healthy lymphocytes that can provide the curative anti-leukemia and antipathogen immune responses that are central to a successful transplantation.
The high selectivity of this photosensitizer may have broad applications, including treatment of blood cancers and autoimmune diseases, due to its rapid production of immune effector cell products with potent antitumor activity and a low potential for toxicity.
This approach could significantly impact clinical outcomes in stem cell transplantation by eliminating the need for prophylactic immune-suppression and offering a safer curative option for more patients, especially those who cannot find a fully HLA-matched donor.
Patients with blood cancers may undergo transplantation of donated T-lymphocytes (T-cells) and stem cells to help eliminate their cancer and generate new, normally functioning blood cells. The donor T-cells may cure the patient of their cancer by identifying and eliminating any residual leukemia that remained in the body, known as the graft-versus-leukemia effect.
However, highly-activated donor T-cells may also cause graft-versus-host disease (GVHD), where donor cells attack the patient’s healthy cells and cause tissue damage. This risk of GVHD increases with higher HLA-disparity between donor and recipient. As a result, many patients who are unable to find a HLA-matched donor experience an even higher risk of GVHD and associated complications.
Current treatment of GVHD consists of high-dose steroids and other immunosuppressive agents that can lead to health complications such as cytomegalovirus reactivation, infection and chronic disease, often resulting in early mortality. Only 50% of patients with severe acute GVHD respond to treatment, and fewer than 30% of patients with steroid refractory GVHD may survive long term.
Preclinical proof of concept trials are completed, and the technology is on track for preIND product development.
• Zachariah McIver, DO, PhD, Department of Hematology & Oncology, Wake Forest University
• Michael Detty, PhD, Department of Chemistry, SUNY Buffalo
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Deepika Poranki, PhD