Search

T cells and NK cells expressing chimeric antigen receptors (CAR) have demonstrated potent clinical efficacy in patients with hematological malignancies. One of the issues to overcome in the treatment of solid tumors using CARs is the lack of a process that generates large amounts of CAR-T cells, reduces cell exhaustion and differentiation, and improves long term survival after infusion into patients. Previously, Torres Chavez et al. demonstrated in a series of in vitro and in vivo experiments, performed in both hematologic and solid tumor models, the profound qualitative impact on CAR-T cell performance after using human platelet lysate (hPL) as a cell growth supplement. T cells expanded with their hPL showed a good proliferative capacity and enhanced long-term in vivo persistence compared to Fetal Bovine Serum (FBS) or human AB Serum (ABS), resulting in superior anti-tumor effects. Additionally, this group demonstrated that the transduction of T cells to generate the CAR-T cells was significantly improved by the use of hPL. 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 Association for the Advancement of Blood & Biotherapies (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, we developed gamma irradiated version of our products, which offer an additional safety measure in the clinic. Previously, we have shown that the use of our platelet lysates has the potential of significantly impacting T cell manufacture by improving the quality and potency of the end product. In this study, we compare the phenotypic profile of different subsets of peripheral blood lymphocytes cultured using our different hPL products versus serum derived products. Additionally we establish a protocol for large scale suspension culture, which could be used for expansion of allogeneic CAR cells. [ABSTRACT FROM AUTHOR]

Abstract Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)–T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Furthermore, the shift toward offshore production may help reduce manufacturing costs. In this article, we examine production costs of an allogeneic CAR-T cell process and the potential differential manufacturing costs between regions. Two offshore locations are compared with regions within the United States. The critical findings of this article identify the COGs challenges facing manufacturing of allogeneic CAR-T immunotherapies, how these may evolve as production is sent offshore and the wider implication this trend could have. [ABSTRACT FROM AUTHOR]