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- Title
Engineering Artificial Antigen-presenting Cells to Express a Diverse Array of Co-stimulatory Molecules.
- Authors
Suhoski, Megan M.; Golovina, Tatiana N.; Aqui, Nicole A.; Tai, Victoria C.; Varela-Rohena, Angel; Milone, Michael C.; Carroll, Richard G.; Riley, James L.; June, Carl H.
- Abstract
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.Molecular Therapy (2007) 15 5, 981–988. doi:10.1038/mt.sj.6300134
- Subjects
CELLULAR immunity; IMMUNOREGULATION; BIOLOGICAL transport; GENETIC transformation; GENETIC engineering; THERAPEUTICS; GENE therapy
- Publication
Molecular Therapy, 2007, Vol 15, Issue 5, p981
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.sj.6300134