Department of Internal Medicine V, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Cells. 2021 Jan 14;10(1):152. doi: 10.3390/cells10010152.
NY-ESO-1-specific T cells have shown promising activity in the treatment of soft tissue sarcoma (STS). However, standardized protocols for their generation are limited. Particularly, cost-effectiveness considerations of cell production protocols are of importance for conducting clinical studies. In this study, two different NY-ESO-1-specific T cell production protocols were compared. Major differences between protocols 1 and 2 include culture medium, interleukin-2 and retronectin concentrations, T cell activation strategy, and the transduction process. NY-ESO-1-specific T cells generated according to the two protocols were investigated for differences in cell viability, transduction efficiency, T cell expansion, immunophenotype as well as functionality. NY-ESO-1-specific T cells showed similar viability and transduction efficiency between both protocols. Protocol 1 generated higher absolute numbers of NY-ESO-1-specific T cells. However, there was no difference in absolute numbers of NY-ESO-1-specific T cell subsets with less-differentiated phenotypes accounting for efficient in vivo expansion and engraftment. Furthermore, cells generated according to protocol 1 displayed higher capacity of TNF-α generation, but lower cytotoxic capacities. Overall, both protocols provided functional NY-ESO-1-specific T cells. However, compared to protocol 1, protocol 2 is advantageous in terms of cost-effectiveness. Cell production protocols should be designed diligently to achieve a cost-effective cellular product for further clinical evaluation.
NY-ESO-1 特异性 T 细胞在软组织肉瘤 (STS) 的治疗中显示出了有前景的活性。然而，其生成的标准化方案受到限制。特别是，细胞生产方案的成本效益考虑对于进行临床研究很重要。在这项研究中，比较了两种不同的 NY-ESO-1 特异性 T 细胞生产方案。方案 1 和 2 之间的主要区别包括培养基、白细胞介素-2 和 retronectin 浓度、T 细胞激活策略和转导过程。根据两种方案生成的 NY-ESO-1 特异性 T 细胞在细胞活力、转导效率、T 细胞扩增、免疫表型和功能方面的差异进行了研究。NY-ESO-1 特异性 T 细胞在两种方案之间表现出相似的活力和转导效率。方案 1 产生了更高数量的 NY-ESO-1 特异性 T 细胞。然而，具有较少分化表型的 NY-ESO-1 特异性 T 细胞亚群的绝对数量没有差异，这些亚群具有有效的体内扩增和植入能力。此外，根据方案 1 生成的细胞显示出更高的 TNF-α生成能力，但细胞毒性能力较低。总体而言，两种方案都提供了功能性的 NY-ESO-1 特异性 T 细胞。然而，与方案 1 相比，方案 2 在成本效益方面具有优势。细胞生产方案应精心设计，以获得具有成本效益的细胞产品，用于进一步的临床评估。
