Turning Research into Practice

Graft-versus-host disease (GVHD) is a risk when patients receive bone marrow stem cells donated from another person. GVHD is a serious complication that limits the use of Bone Marrow Stem Cell (BMSC) transplantation in patients with blood cancers. GVHD occurs when the donor’s immune cells attack the patient’s normal tissues (skin, liver, gut). GVHD can be acute or chronic. Its severity depends on the differences in tissue type between patient and donor. Acute GVHD can occur soon after the transplanted cells begin to appear in the recipient and can range from mild to severe and can be life-threatening.

The Role of CCR5 in GVHD

The CCR5 receptor, the target for Leronlimab, is an important mediator of GVHD, especially in the organ damage that is the usual cause of death.  The CCR5 receptor on engrafted cells is critical for the development of acute GVHD and by blocking this receptor from recognizing certain immune signaling molecules appears to be a viable approach to mitigating acute GVHD. The potential of Leronlimab to prevent this life-threatening condition could help extend the use of BMSC transplantation to effectively treat more patients. 

Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted bone marrow stem cells.

Leronlimab’s Significant Inhibitory Effect on GVHD

CytoDyn’s research in association with Dr. Daniel Lindner, M.D., Ph.D. of the Department of Translational Hematology and Oncology Research, The Cleveland Clinic, showed that when immunocompromised mice transplanted with human BMSCs received Leronlimab at a dosing schedule that approximates that being used in the ongoing human clinical trial, the mice showed successful engraftment of human hematopoietic (blood-forming) cells without any signs of GVHD. At the same time, control mice all exhibited classical signs of GVHD and none survived (p˂0.01). A 10-fold reduction in PRO 140 dosage still showed a significant inhibitory effect on GVHD in treated mice but to a lesser extent. The study has been published online in the peer-reviewed journal, Biology of Blood and Marrow Transplantation, PRO 140 Monoclonal Antibody to CCR5 Prevents Acute Xenogeneic Graft-versus- Host Disease in NOD-scid IL-2Ry Mice, February 2018 Volume 24, Issue 2.

The FDA has granted orphan drug designation to CytoDyn for the prevention of acute graft-versus-host disease (GVHD).

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