Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

Abstract

Abstract. Cell-based adoptive immunotherapy for the treatment of various cancer types has attracted the attention of scientists. However, due to the absence of unitary standard protocols to produce large quantities of clinical-grade effector cells, it remains challenging to translate the experimental findings into clinical applications. The present study used methods complying with good manufacturing practice to induce effector cells from human peripheral blood mononuclear cells (PBMCs) of healthy donors by interleukin-2 and anti-Her-2 antibody with or without anti-CD3 antibodies (OKT3). The results indicated that the addition of OKT3 resulted in a greater expansion of the total cells and CD8 + T cells, and primarily induced the PBMCs to differentiate into CD3 + T cells. Regardless of the presence of OKT3, the expression of activating receptor of natural killer (NK) group 2, member D, and the inhibitory receptors of CD158a and CD158b on NK cells and NKT cells was increased, while the expression of NKp46 was inhibited on NK cells, but not on NKT cells. Furthermore, OKT3 did not affect the toxicity of the effector cells. Subgroup analysis indicated that although a variation of the composition of effector cells was present in different individuals under identical culture conditions, consistent marker expression on effector cells and target cell-killing effects were observed in different subgroups treated with or without OKT3. Furthermore, western blot analysis indicated that OKT3, apart from its involvement in cell cycle regulation, affects transcription and protein translation during processes of proliferation and differentiation. The present study provided experimental data regarding the production of effector cells for adoptive immunotherapy as a clinical application.

Coating Nanoparticles with Gastric Epithelial Cell Membrane for Targeted Antibiotic Delivery against Helicobacter pylori Infection

“…In this regard, the rapid development of ex vivo cell expansion technology may be able to supply sufficient amount of cell membrane materials for clinical studies. [47, 48] Meanwhile, the well-established genetic engineering approaches would allow for on-demand cell membrane modification for specific functions and uses. [49] The advancement of these technologies together would offer a promising prospect to the translation of AGS-NPs and the cell membrane-coating technology in general.…”

Clinical grade production of IL‐15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post‐transplant cyclophosphamide

“…In terms of manufacturing, in response to the need for highly purified activated NK cell products, many NK cell-based GMP protocols have been developed and different products have been described: Cytokine Induced Killer cells, [38][39][40] NKAE Cells, 15 MG401 cells, 41 NKF-NK, 42 NK-15 cells, 15 NK-IL21. 34 However, many of these protocols require expensive, complex manufacturing procedures and time-consuming long culture periods [38][39][40][41][42][43][44][45][46][47] that may be detrimental for their application in routine clinical practice.…”

Vai trò của hạt từ phủ kháng thể CD3/CD28 và IL-2 lên sự tăng sinh tế bào đơn nhân máu ngoại vi người (PBMC)

“…Số lượng hạt so với tế bào, gọi là tỉ lệ hạt-tế bào (bead-to-cell, B:C), là một yếu tố quyết định đến cường độ tín hiệu và sự tăng sinh của tế bào. Nếu tỉ lệ hạt-tế bào quá cao sẽ dẫn đến suy yếu tế bào T, ngược lại tỉ lệ quá thấp lại thất bại trong việc kích hoạt tế bào T, cả hai yếu tố trên dẫn đến việc kích hoạt tăng sinh tế bào T dưới mức tối ưu (Shi et al, 2013;Yu et al, 2017).…”