2-Se-Cl: Novel Photosensitizer Prevents Graft-Versus-Host Disease

A novel proprietary photosensitizer that uses highly selective photodepletion to prevent graft-versus-host disease in stem cell transplant patients with cancers of the blood. The photosensitizer selectively eliminates the donor T-cells that cause graft-versus-host disease, which may lead to longer survival for stem cell transplant recipients and remove the need for potentially harmful prophylactic immune-suppression.

Problem

Patients with cancers of the blood may undergo transplantation of donated stem cells to generate new, normally-functioning bone marrow. In addition to protecting from infection, the donor T-lymphocytes fight cancer cells that might have remained in the body, known as the graft-versus-leukemia effect. However, highly-activated donor T-lymphocyte cells can also cause graft-versus-host disease, where donor cells recognize the patient’s cells as foreign and cause tissue damage. This condition occurs in 60 to 80% of patients undergoing bone marrow transplants. Less than 30% of patients who develop severe acute graft-versus-host disease survive long-term

Current treatment consists of high-dose steroids and other immunosuppressive agents that can lead to health complications such as cytomegalovirus reactivation, infection, and chronic disease which can result in early mortality.

Solution

Researchers at Wake Forest Baptist Medical Center have developed a highly selective photodepletion for activated T-cells that uses a novel proprietary photosensitizer called 2-Se-Cl. Such selective photodepletion eliminates T-lymphocytes that cause harmful graft-versus-host disease, keeping healthy lymphocytes that can mediate anti-leukemia, antiviral and antifungal immune responses. This may lead to improved safety and efficacy of stem cell transplants and ultimately improves survival compared to conventional approaches.

Competitive Benefits

  • Ex-vivo application of the novel photosensitizer prevented lethal graft-versus-host disease and improved survival after stem cell transplantation in an animal model of the disease
  • Photosensitizer is highly selective and maintains antiviral and antileukemic immune responses after photodepletion
  • Selective photodepletion of activated T Lymphocytes leads to the reconstitution of antipathogen and antitumor immunity that eliminates infection and cancer and improves survival
  • Photosensitizer may make unrelated and HLA-mismatched transplants a safer curative option for more patients
  • Prevention of graft-versus-host disease will result in significant financial savings due to the high cost of treating the disease

Inventors

  • Zachariah McIver, MD, Department of Hematology & Oncology
  • Michael Detty, PhD, Department of Chemistry, SUNY Buffalo

Application Fields

Leukemia, lymphoma, myelodysplastic syndromes

Stage of Development

Preclinical proof of concept trials are completed, and the technology is on track for preIND product development.

Keywords

Angiotensin-(1-7), TCAng05, MAS receptor, agonist, breast cancer, prostate cancer, sarcoma, non-toxic chemotherapeutic

Patent Status

US7906500 B2
WO 2015187940A1

Publications

McIver, ZA et al. Targeting T Cell Bioenergetics by Modulating P-Glycoprotein Selectively Depletes Alloreactive T Cells To Prevent Graft-versus-Host Disease. J. Immunol. 2016; 197(5): 1631-41.

Licensing Contact

Peter Golikov, MS, MBA, CLP
Licensing Director, Center for Technology Innovation & Commercialization
pgolikov@wakehealth.edu
+1.336.713.1664

Ref #: WFU 14-85

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