Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules.
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.
Suhoski
Megan M
MM
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104-5160, USA.
Golovina
Tatiana N
TN
Aqui
Nicole A
NA
Tai
Victoria C
VC
Varela-Rohena
Angel
A
Milone
Michael C
MC
Carroll
Richard G
RG
Riley
James L
JL
June
Carl H
CH
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D016086:Lentivirus / Q000235:genetics; D008858:Microscopy, Phase-Contrast; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000954:Antigens, Surface; D018106:CD28 Antigens; D016207:Cytokines; D017452:Receptors, IgG; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9