Abstract 5252: Expansion of human T cells and NK cells for chimeric antigen receptor based therapies using human platelet lysate

Abstract

Abstract 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 a gamma irradiated version of our products, which offers an additional safety measure in the clinic. Our data from experiments performed using human CD3+ and purified NK cells from donor peripheral blood suggests that our human platelet lysates offer an improved cell phenotype and expansion capacities versus serum derived products, but also versus other platelet lysates on the market. PLTGold® and PLTGold®-GI efficiently promote cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, our hPLs are suitable for suspension culture, potentially facilitating the large-scale expansion of allogeneic CAR cells. The use of our platelet lysates has the potential of significantly improving CAR-T and CAR-NK manufacture, but also the outcome of the therapy itself by improving the quality and potency of the end product. Citation Format: Vanesa Alonso-Camino, William Mirsch. Expansion of human T cells and NK cells for chimeric antigen receptor based therapies using human platelet lysate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5252.