allogeneic lymphocyte-licensed dcs expand t cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors

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ID: 216876
2014
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Abstract
Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the “rapid expansion protocol” (REP), which utilizes OKT-3, interleukin (IL)-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion. Here, we demonstrate that when irradiated and preactivated allosensitized allogeneic lymphocytes (ASALs) are used as helper cells to license OKT3-armed allogeneic mature dendritic cells (DCs), together they expand target T cells of high quality. The ASAL/DC combination yields an enriched Th1-polarizing cytokine environment (interferon (IFN)-γ, IL-12, IL-2) and optimal costimulatory signals for T-cell stimulation. When genetically engineered antitumor T cells were expanded by this coculture system, they showed better survival and cytotoxic efficacy under oxidative stress and immunosuppressive environment, as well as superior proliferative response during tumor cell killing compared to the REP protocol. Our result suggests a robust ex vivo method to expand T cells with improved quality for adoptive cancer immunotherapy.
Reference Key
jin2014molecularallogeneic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Chuan Jin, Di Yu, Victoria Hillerdal, AnnaCarin Wallgren, Alex Karlsson-Parra, Magnus Essand
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Journal international journal of zoology
Year 2014
DOI
10.1038/mtm.2014.1
URL
http://www.sciencedirect.com/science/article/pii/S2329050116300754
Keywords
geneticscytology

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