Cell Therapy - Allogeneic Cell Therapy

Allogeneic Cell Therapy

Allogeneic cell therapy involves harvesting donor cells from one, or a few, universal donors. These cells will be expanded in a manufacturing facility and cryopreserved for later manipulation or as therapeutic doses. This allogeneic approach utilizes cell types that do not elicit immune responses upon implantation and therefore have the potential to treat hundreds of patients from a single manufactured lot of cells. The allogeneic methodology fits the pharmaceutical model of drug manufacturing because the product can be readily available for “off the shelf” distribution.

Currently, there are numerous clinical trials involving allogeneic-derived adult stem cells. Increasingly, mesenchymal stem cells are being proposed as agents for cell-based therapies, due to their plasticity, established isolation procedures, and capacity for ex vivo expansion. Manufacturing models are in development for bone marrow mesenchymal stem cells (such as Osiris’ Prochymal platform) and multipotent adult progenitor cells (MSCs, such as Athersys’ MultiStem platform). Other cell types included in this model are human embryonic stem cells (hESCs, such as Geron’s hESC-based platform of differentiated cells, described further in Section 2.1), hematopoietic stem cells (HSCs), as well as engineered cells used in tissue grafts. Therapeutic targets for such allogeneic therapies include graft versus host disease, myocardial infarction, central nervous system disorders, stroke, diabetes, osteoarthritis, and other diseases.

Challenges to the allogeneic approach primarily reside in the manufacture of the cellular product. Large numbers of cells (greater than 1011-12) must be produced per lot to satisfy the larger dosing requirement (which may exceed 106 cells/kg/dose). The cells must be efficiently expanded in culture while retaining their proper cell characterization profile and efficacy. In addition, the cellular product must be amenable to cryopreservation and subsequent revival in order for the “off the shelf” production model to be successful. The successful manufacture of these products must also rely on a stringent quality control policy to demonstrate lot-to-lot consistency and safety.