The SAGE Encyclopedia of Stem Cell Research. Группа авторов

      Cellerant Therapeutics

      Cellerant Therapeutics

      204

      206

      Cellerant Therapeutics

      Cellerant Therapeutics is a clinical-stage biotechnology company whose focus is on the regulation of the hematopoietic system. Cellerant Therapeutics was founded in 2005 and is headquartered in San Carlos, California. Cellerant Therapeutics Inc. is a privately held, venture capital–backed corporation with investors including Allen & Company LLC, BD Ventures LLC, CX Venture Group, Eminent Venture Capital, GBR Investments LLC, MPM Capital, Rockbridge Growth Equity, and Sagamore Bioventures (formerly Novel Bioventures).

      Cellerant Therapeutics is developing human stem cell and antibody therapies for oncology applications and blood related disorders. The lead product for Cellerant Therapeutics is CLT-008, which is currently associated with two Phase I clinical trials involving patients with hematological malignancies. Cellerant has also produced a cancer stem cell (CSC) antibody discovery program that is focused on the treatment of acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome.

      CLT-008 is an off-the-shelf cell-based medicine that can facilitate engraftment in cord blood transplants (CBT) and treat neutropenia. CLT-008 consists of myeloid progenitor cells. Progenitor cells, unlike stem cells, can create a large number of mature cells but cannot self-renew. Progenitor cells are also limited to creating a smaller subset of mature cells than stem cells. Myeloid progenitor cells are cells of the blood-forming system that have lost the stem cell ability to self-renew and are restricted to creating mature myeloid cells, which include red blood cells, platelets, and the immune cells that fight bacterial and fungal infections. Myeloid progenitor cells cannot create lymphoid cells, including the T cells that cause graft-versus-host disease (GVHD). After infusion of myeloid progenitor cells, they create a burst of mature cells and then die after about 45 days. CLT-008 contains only early- to late-stage myeloid progenitor cells because it starts its manufacturing process with highly purified blood-forming stem cells. Therefore, CLT-008 does not contain the mature T cells that can cause immune reactions.

      CLT-008 is intended to act as a truly universal bridging therapy. It does not require immune system matching, creates mature cells for a defined period of time, and then clears from the patient like a drug. CLT-008 was designed by Cellerant Therapeutics for use in the treatment of neutropenia, wherein patients lack mature granulocytes and macrophages to fight off opportunistic infections. When CLT-008 is infused, the cells are designed to differentiate to create a large number of mature daughter cells. At this writing, Cellerant Therapeutics is initiating Phase I clinical trials evaluating safety of CLT-008 in patients receiving cord blood transplant for the treatment of hematologic malignancies.

      Cellerant Therapeutics is also pursuing the use of CLT-008 to treat victims of radiation exposure in a nuclear terror incident or nuclear accident. In the event of a nuclear detonation or nuclear power plant explosion, thousands of people may die from radiation exposure. In a highly populated area, the predicted number of casualties could range between 10,000 and 190,000 people. Some of these injuries are caused by the blast and heat, others from crushing injuries. However, the greatest number of casualties is caused by the effects of radiation. The human hematopoietic (blood-forming) system is especially susceptible to radiation injury.

      As a result of radiation injury to the blood-forming system, victims suffer from a lack of the cells that deliver oxygen (red blood cells), cells that detect and eliminate infectious agents (white blood cells), and cell components that promote blood clot formation (platelets). This set of symptoms is generally referred to as acute radiation syndrome (ARS). While some victims of moderate to high levels of radiation are beyond saving, most victims will have received enough radiation to injure but not kill their bone marrow. They will recover from their injuries, but face a 30–60-day period during which they cannot fight infections and are prone to uncontrolled bleeding and anemia. In order to remain alive until their hematopoietic system recovers, they must receive supportive care. However, the very nature of a disaster such as this will greatly decrease the availability and access to high-level supportive care.

      Many of the victims of the Chernobyl disaster, for example, would have survived with the appropriate supportive care, but such care was not possible in the field. Two major advantages make CLT-008 ideal for the treatment of a large number of ARS victims because (1) treatment can be delayed until disaster response teams are in place and victims appropriately triaged, and (2) CLT-008 can be administered in the field and used even when there is little available infrastructure to provide standard supportive care and hospitalization. CLT-008 (myeloid progenitor cells for infusion) has the potential to rescue a substantial number of ARS victims.

      Derived from adult blood-forming stem cells, CLT-008 has been shown in animal models to be effective in preventing lethal bacterial and fungal infections after radiation exposure. CLT-008 is an off-the-shelf frozen product that can be shipped to the disaster site, thawed, and infused into patients through a standard IV line. Once infused, CLT-008 rapidly proliferates into infection-fighting neutrophils and platelets necessary for blood clotting. CLT-008 is designed for use even if administered several days after exposure. It can be stockpiled in a secure location, ready for rapid delivery to the site of an attack. CLT-008 acts as a temporary therapy until the individual’s own blood-forming system recovers and begins to generate its own infection-fighting and clotting cells. And it works synergistically with growth factors like G-CSF to provide protection quickly.