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  • [ Recombinant Protein ] A lifesaver: IL-18 overcomes the limitation of γδT cells’ short lifespan.

[ Recombinant Protein ] A lifesaver: IL-18 overcomes the limitation of γδT cells’ short lifespan.

2023-01-03

What’s the IL-18 and its ability?

The proinflammatory cytokine interleukin-18 (IL-18, also called interferon-gamma inducing factor) is produced by macrophages, dendritic cells, and other cells. IL-18 is a member of the IL-1 superfamily and can induce several cells to produce different cytokines in response to various situations. [1-4]

How does IL-18 be used in cell therapy?

♦ γδT cells
Due to the γδT cells MHC-unrestricted character, studies both in vivo and in vitro have demonstrated that γδT cells may recognize a variety of tumor cells and perform anticancer functions. [5] However, the effectiveness of γδT cells therapy was limited by the survival and proliferation of adoptively transferred γδT cells in vivo. [6, 7] To increase the therapeutic benefits of γδT cell-based therapies, novel approaches are therefore required to differentiate and produce long-lived anti-tumor γδT cells. Compared to γδT cells that were treated without IL-18, those that were incubated with IL-18 produced much more GM-CSF, IFN-γ, and TNF-α and enhanced the cytotoxic activity toward the tumor cells. The growth of a mesothelioma xenograft in mice was slowed and they demonstrated high cytotoxicity against tumor cells, including mesothelioma cells. These findings suggest that IL-18 successfully boosts γδT cells growth with substantial anticancer activity. [8] Furthermore, the studies also found a very powerful ex vivo-expanded Vγ9Vδ2 T cell activator which is the combination of IL-12 and IL-18, and these two cytokines are capable of increasing the level of granzymes and IFN-γ together while decreasing the expression of the co-inhibitory receptor, the B- and T-lymphocyte attenuator (BTLA). [9]




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Ref.
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  7. Sakamoto M, Nakajima J, Murakawa T, Fukami T, Yoshida Y, Murayama T, Takamoto S, Matsushita H, Kakimi K. Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: a phase I clinical study. J Immunother. 2011 Mar;34(2):202-11.
  8. Li W, Kubo S, Okuda A, Yamamoto H, Ueda H, Tanaka T, Nakamura H, Yamanishi H, Terada N, Okamura H. Effect of IL-18 on expansion of gammadelta T cells stimulated by zoledronate and IL-2. J Immunother. 2010 Apr;33(3):287-96.
  9. Domae E, Hirai Y, Ikeo T, Goda S, Shimizu Y. Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells. Oncotarget. 2017 Jul 11;8(28):45928-45942.
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