Trillium Therapeutics Inc (TRIL)

[biocqr]

CD47> Stanford mouse study using anti-CD47 (no chemo) for HSC/bone marrow transplants...

Bone Marrow Transplants – Without Chemotherapy Side Effects
http://acsh.org/news/2016/08/11/bone-marrow-transplants-without-chemotherapy-side-effects/

If the therapy applies to humans, it could mean cures for autoimmune diseases like lupus and multiple sclerosis, safer organ transplants, and even cures for cancers – without damage to organs.

They started with an antibody against a cell surface protein called c-kit, which is a primary marker of blood stem cells. Attaching the antibody to c-kit resulted in depletion of blood stem cells in immune-deficient mice. “However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said Stanford research associate Akanksha Chhabra, PhD, in their statement. So they combined it with antibodies and agents that block the CD47 cell surface protein. Blocking CD47 liberated macrophages to “eat” target cells covered with c-kit antibody, Chhabra said.

Once the CD47 marker was blocked and the antibody was attached to c-kit proteins, the immune system effectively depleted the animals’ blood-forming stem cells, clearing the way for transplanted blood stem cells from a donor to take hold in the bone marrow and generate a whole new blood and immune system. After that, a patient’s blood and immune system can safely be replaced, so any disease caused by the patient’s own blood and immune cells could potentially be cured by a one-time application of blood stem cell transplantation, the authors say. Safely replacing a patient’s blood and immune cells will get rid of the cells that attack their own tissues and produce disease like rheumatoid arthritis and Type 1 diabetes.

This success in mice raises hopes that similar techniques will succeed in human patients. “If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20 percent to effectively zero,” said Judith Shizuru, MD, PhD, professor of medicine at Stanford.

study...

Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy
http://stm.sciencemag.org/content/8/351/351ra105
Quote:
Abstract
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti–c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti–c-Kit conditioning to fully immunocompetent mice. The combined treatment leads to elimination of >99% of host HSCs and robust multilineage blood reconstitution after HSC transplantation. This targeted conditioning regimen that uses only biologic agents has the potential to transform the practice of HSC transplantation and enable its use in a wider spectrum of patients.