Data collection in expanded access: real-world examples 27 TABELECLEUCEL FOR EPSTEIN-BARR VIRUS-DRIVEN DISEASES Background The second real-life example concerns a living cell therapy called tabelecleucel, developed by Atara Biotherapeutics.55 Atara Biotherapeutics and myTomorrows initiated an expanded access program to provide tabelecleucel to patients in Europe.56 Tabelecleucel (also known as tab-cel®) is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates cells infected with the Epstein-Barr Virus. At the initiation of the expanded access program, tabelecleucel was in late clinical development for patients with post-transplant lymphoproliferative disorders (PTLDs). PLTD is a serious and potentially fatal complication in patients that have undergone a transplant, either allogeneic stem cell or solid organ. These patients are severely immunocompromised and thus may not be able to adequately control the virus, which may lead to lymphoproliferation and PTLD. In the program, requests for tabelecleucel could only be accepted if patients were relapsed or refractory to standard treatment options, such as rituximab or chemotherapy regimens, or were ineligible for registered therapies. Compared with the production of pritelivir in the previous chapter, the production of tabelecleucel is complex. Tabelecleucel is produced from T-cells harvested from human donors. The final products are tested for their capacity of eliminating Epstein-Barr Virus-positive cells in a Human Leucocyte Antigen (HLA)-restricted manner. By producing tabelecleucel with T-cells from different donors, various different cell lines of therapy could be pre-produced and stored in an inventory, making tabelecleucel a cell therapy that is available off-the-shelf. The product is selected for each patient from the existing inventory based on appropriate HLA restriction and allele profile, hence the HLA genotype information from patient and transplant donor is mandatory. Based on response assessment patients could potentially switch to a different cell line with a different HLA restriction as defined in the treatment plan. Being a cell therapy, there are unique requirements for the storage, handling, transportation, and administration of tabelecleucel. For example, the product is required to be monitored and packaged to ensure stability under extremely low temperatures (≤ -150°C), a process known as cold-chain shipment. As a consequence, only hospital sites with dedicated licenses to meet regulatory standards were allowed to participate in the expanded access program and training for product administration was required to ensure the safe and effective delivery of tabelecleucel to patients.
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