[HTML][HTML] Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules

MM Suhoski, TN Golovina, NA Aqui, VC Tai… - Molecular Therapy, 2007 - cell.com
MM Suhoski, TN Golovina, NA Aqui, VC Tai, A Varela-Rohena, MC Milone, RG Carroll…
Molecular Therapy, 2007cell.com
To facilitate the therapeutic application of antigen-presenting cells (APCs), we have
developed a cell-based artificial APC (aAPC) system by engineering K562 cells with
lentiviruses to direct the stable expression and secretion of a variety of co-stimulatory
molecules and cytokines. Here we report the use of a combinatorial lentiviral gene transfer
approach to achieve long-term stable expression of at least seven genes in the K562
parental cell line. Expression of various combinations of genes on the aAPC enables the …
To facilitate the therapeutic application of antigen-presenting cells (APCs), we have developed a cell-based artificial APC (aAPC) system by engineering K562 cells with lentiviruses to direct the stable expression and secretion of a variety of co-stimulatory molecules and cytokines. Here we report the use of a combinatorial lentiviral gene transfer approach to achieve long-term stable expression of at least seven genes in the K562 parental cell line. Expression of various combinations of genes on the aAPC enables the precise determination of human T-cell activation requirements, such that aAPCs can be tailored for the optimal propagation of T-cell subsets with specific growth requirements and distinct functions. The aAPCs support ex vivo growth and long-term expansion of functional human CD8 T cells without requiring the addition of exogenous cytokines, in contrast to the use of natural APCs. Distinct populations of T cells can be expanded with aAPCs expressing CD137L (4-1BBL) and/or CD80. Finally, the aAPCs provide an efficient platform to expand genetically modified T cells and to maintain CD28 expression on CD8 T cells. Therefore, K562-based aAPCs have therapeutic potential for adoptive immunotherapies and vaccinations.
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