Talaris scientists have discovered a way to use the body’s immune system to help it accept organ transplants by selectively infusing specific cells from the organ donor into the organ recipient, much like a blood donation.
The likelihood of an organ transplant recipient spontaneously developing tolerance to the donated organ as a result of withdrawal of immunosuppression (referred to as “operational tolerance”) is extremely low. Fewer than 100 cases of operational tolerance have been documented out of hundreds of thousands of solid organ transplants performed worldwide since 1955, and in many of those cases this tolerance was not durable.
Scientists have known for decades that bone marrow-derived stem cells from a healthy donor (referred to as an allogeneic stem cell transplant) have the potential to induce durable tolerance to transplanted organs in the transplant recipient. However, the significant risks associated with a conventional stem cell transplant from a donor who is not a perfect immune system match to the recipient, and the unpredictability of achieving durable engraftment of the donor’s stem cells in the recipient, have prevented widespread use. Conventional allogeneic stem cell transplant also brings a risk of graft versus host disease, which is a serious condition whereby the donor’s immune cells attack the recipient’s tissues.
The Promise of Chimerism
The Talaris therapy seeks to proactively promote immune tolerance in the recipient by inducing “chimerism” in the recipient’s immune system, while minimizing the risk of graft versus host disease. “Chimerism” refers to a state where both the donor’s and recipient’s immune cells co-exist durably in the transplant recipient (creating, in effect, a “dual” immune system in the transplant recipient). Chimerism can be measured by a simple blood test, and, if durable for more than six months after the organ transplant, can be a good predictor of the ability to wean a transplant recipient off all immunosuppression by twelve months post-transplant (and potentially allow that patient to stay off all immunosuppression).
The goal of administering FCR001 to the recipient is to enable the donor’s stem cells to engraft into the recipient’s bone marrow, in order to create a durable, “dual” immune system. In combination with an organ transplant, a single dose of FCR001 may enable the recipient’s immune system to recognize the donated organ as “self.” This potentially allows the transplant recipient’s immune system to accept the transplanted organ without the need for lifelong immunosuppression. We believe that our approach may also have the potential to restore self-tolerance to patients with certain types of auto-immune or immune-mediated disorders (where the patient has lost tolerance to some aspect of “self”) and to correct certain types of genetic blood disorders.
“As a transplant surgeon, I have seen firsthand the life-saving benefits of organ transplantation as well as the challenges our patients face due to their lifelong dependence on immunosuppressive drugs. It has been immensely gratifying to see our research discovery being applied to improve the lives of kidney transplant recipients.”
— Suzanne Ildstad, Founder and Chief Scientific Officer
The Discovery of Facilitating Cells
The Talaris platform technology builds upon our founder Dr. Suzanne Ildstad’s discovery of the Facilitating Cell. These cells exist in the bone marrow and are distinct from stem cells. Pre-clinical research on the Facilitating Cell has shown that they act as nurse cells that nurture stem cells in the bone marrow. After a stem cell transplant, Facilitating Cells help the transplanted stem cells migrate to the recipient’s bone marrow, where they produce immune cells and other blood cells. When combined with other cells through our proprietary process, Facilitating Cells help to promote engraftment of the donor’s cells in the recipient’s bone marrow.
We have also shown that Facilitating Cells help to promote certain types of cells and processes in the recipient that enhance the development of immune tolerance and reduce the risk of graft versus host disease. We have demonstrated that FCR001 allows candidates for bone marrow transplants to receive stem cells safely from unmatched and unrelated donors, with much lower risks than a traditional allogeneic bone marrow transplant.
How FCR001 works
For some scientific publications on Facilitating Cells, click here.
Our Manufacturing Process
Talaris has developed a proprietary process to make FCR001. We rigorously control the product and process at every step of the way, from donor to recipient. The process begins with cells collected from the donor’s blood via a standard mobilization and apheresis procedure, at least a few weeks before the kidney transplant. These cells are shipped to our centralized, cGMP cell processing facility, where highly trained personnel process the donated cells to remove certain potentially harmful cell populations, enrich for stem cells and Facilitating Cells, and then perform a series of analytical studies to confirm the quality of the product. Each FCR001 product is customized to the particular recipient. The final product is frozen and then shipped to the clinical site, where it is stored until it can be administered to the transplant recipient.
Donor undergoes mobilization and apheresis as an outpatient to collect cells for the Talaris product.
Donor’s cells are refrigerated and shipped to Talaris’ GMP cell processing facility.
Highly trained manufacturing team utilizes proprietary Talaris technology to remove certain types of undesirable cells and enrich the product for stem cells and facilitating cells.
Final product is frozen and shipped to the clinical site, where it can be stored until needed.
Our Phase 2 Results
Talaris has followed the patients in our Phase 2 study for an average of over 4.5 years, and for as long as 9 years. Our data indicate the potential of successfully tolerized transplant patients to remain off chronic immunosuppression durably without rejecting their organ.
We believe that our technology has the potential to benefit patients in other transplant settings as well as patients who suffer from difficult-to-treat auto-immune diseases or immune-mediated diseases. Click here for a link to our pipeline.