ABSTRACT
Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumorassociated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells.
ABSTRACT
Background & Aim: Mill Creek’s human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food & Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. However, over the past few decades, the number of emerging infectious diseases that spread to people has increased. Even though transmission of Covid-19 and other potential emergent pathogens via blood transfusion has not been documented, adventitious agents remain a concern. For that reason, pathogen reduction processes are necessary to improve the safety profile of blood-derived products used in the manufacture of cellbased therapies. One of these processes is the pathogen reduction through gamma irradiation. Methods, Results & Conclusion: Previously, we validated a process to produce gamma irradiated human platelet lysate. To be able to release the gamma irradiated product as a pathogen reduced product, we additionally performed a viral clearance study, which determined the efficacy of the process to actually reduce a potential viral contaminant. Here, we present the results obtained from the viral clearance study performed on our gamma irradiated hPL, and from the expansion of different types of therapeutic cells using our gamma irradiated hPLs, which showed unprecedented levels of product quality and efficiency. Our products are a game changer for the growing market of cell base therapies bioprocessing and manufacturing.