Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

Gong, Weijuan; Ming-chun, JI; Cao, Zhengfeng; Wang, Liheng; Qian, Yayun; Hu, Mengjie; Li, Qian; Pan, Xingyuan

doi:10.1038/cmi.2008.6

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…Recombinant soluble beta 2 microglobulin (b2m) protein was produced and purified in our lab, as previously described. 18 The following antibodies were used for immunophenotypic characterization of activated and expanded cells: phycoerythrin (PE)-conjugated anti-CD3; fluorescein isothiocyanate (FITC)-, Alexa 647-and PE-Cy5-conjugated anti-CD56; PEconjugated anti-CD69; PE-conjugated anti-NKG2D; FITC-conjugated anti-CD16; PE-and FITC-conjugated anti-IFN-c; Alexa 647-conjugated anti-CD107a; allophycocyanin-conjugated anti-NKG2A; Alexa 647 antiNKp46; PE-conjugated anti-CD226; FITC-conjugated anti-CXCR3; and FITC-conjugated anti-CCR7. All antibodies were purchased from eBioscience (San Diego, CA, USA) or Biolegend (San Diego, CA, USA).…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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Major histocompatibility complex (MHC) class I chain-related protein A (MICA), which is a ligand for human NKG2D, is expressed by a variety of epithelial tumor cells and promotes the activation of natural killer (NK), CD8 1 and cd-T cells. Although ectopic expression of MICA on tumor cells elicits anti-tumor responses, soluble MICA downregulates the activities of lymphocytes. In this study, we showed that recombinant, immobilized MICA (iMICA) molecules coated on plastic wells weakly promote peripheral NK cell activation, secretion of interferon (IFN)-c and degranulation without inducing apoptosis. In addition, iMICA synergized with IL-15 and soluble 4-1BB ligand (s4-1BBL) to expand NK cells 25-to 42-fold in a 13-day culture, whereas NK cells stimulated only with IL-15 and s4-1BBL expanded 10-to 16-fold. In contrast to NK cells expanded by IL-15 and s4-1BBL stimulation, NK cells expanded long term in the presence of iMICA exhibited increased cytotoxicity against leukemia cells. These results suggest that large numbers of NK cells with high cytotoxicity can be generated by stimulation with IL-15 and s4-1BBL in the presence of iMICA and that these cells can be used for adoptive cancer immunotherapy. Studies on the 4-1BB signaling pathway have shown that ligation of 4-1BB promotes the survival and multiplication of CD8 1 T and NK cells. 6 IL-15 is essential for the development and function of NK cells. 7 Coculture of NK cells with K562 cells ectopically coexpressing 4-1BB ligand (4-1BBL) and membrane-bound IL-15 effectively promotes the expansion of NK cells in vitro and mediates their cytotoxicity against some leukemia cells. 8,9 In addition, IL-15 upregulates the expression of NKG2D on NK and T cells, even in the presence of soluble NKG2DL. 10 IL-15 and NKG2D signals cross-regulate each other and

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Section: Reagents and Antibodiesmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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“…Growth of ex vivo DCs is both labour and resource intensive. The requirement to generate a tailor made vaccine for every patient 6,7 means that ex vivo DCs are not economically sustainable. The aforementioned inefficiencies in the production of ex vivo DC's has inspired investigators to design articial antigen-presenting cells (aAPCs) as alternatives.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

et al. 2013

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A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length $200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

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“…Several modifications have since been made on this platform permitting expansions of specific T-cell populations. Accordingly, the K32 cells have been engineered to express a wide array of costimulatory molecules, including CD40, CD64, CD40L, CD70 [73], CD80, CD83, CD86, CD137L [74], ICOSL, GITRL, CD134L, to facilitate proliferation of specific immune cell types including T and NK cells [75][76][77][78] (Table 2). This K-32 system has been developed under cGMP conditions and implemented for clinical use ( Table 2).…”

Section: Aapc For Non-specific Expansion Of T-cellsmentioning

confidence: 99%

Artificial Antigen Presenting Cells: An Off the Shelf Approach for Generation of Desirable T-Cell Populations for Broad Application of Adoptive Immunotherapy

Selvakumar

O’Reilly³

2015

Adv Genet Eng

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Adoptive transfer of antigen specific T-cells can lead to eradication of cancer and viral infections. The broad application of this approach has further been hampered by the limited availability of adequate numbers of T-cells for treatment in a timely manner. This has led to efforts for the development of efficient methods to generate large numbers of T-cells with specificity for tumor or viral antigens that can be harnessed for use in cancer therapy. Recent studies have demonstrated that during encounter with tumor antigen, the signals delivered to T-cells by professional antigen-presenting cells can affect T-cell programming and their subsequent therapeutic efficacy. This has stimulated efforts to develop artificial antigen-presenting cells that allow optimal control over the signals provided to T-cells. In this review, we will discuss the cellular artificial antigen-presenting cell systems and their use in T-cell adoptive immunotherapy for cancer and infections.

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Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

Cited by 12 publications

References 30 publications

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

Artificial Antigen Presenting Cells: An Off the Shelf Approach for Generation of Desirable T-Cell Populations for Broad Application of Adoptive Immunotherapy

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