[ 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 cellsDue 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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→ Croyez GMP ® IL-3 (Interleukin-3), Human
→ Croyez GMP ® IL-4 (Interleukin-4), Human
→ Croyez GMP ® IL-6 (Interleukin-6), Human
→ IL-12 p70 (Interleukin-12 p70), Human (mammalian cell expression)
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Ref.
- Carroll HP, Paunovic V, Gadina M. Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity. Rheumatology (Oxford). 2008 Sep;47(9):1269-77.
- Volin MV, Koch AE. Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. J Interferon Cytokine Res. 2011 Oct;31(10):745-51.
- O'Brien LC, Mezzaroma E, Van Tassell BW, Marchetti C, Carbone S, Abbate A, Toldo S. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol Med. 2014 Jun 12;20(1):221-9.
- Swain SL. Interleukin 18: tipping the balance towards a T helper cell 1 response. J Exp Med. 2001 Aug 6;194(3):F11-4.
- Gober HJ, Kistowska M, Angman L, Jenö P, Mori L, De Libero G. Human T cell receptor gamma delta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med. 2003 Jan 20;197(2):163-8.
- Lo Presti E, Pizzolato G, Gulotta E, Cocorullo G, Gulotta G, Dieli F, Meraviglia S. Current Advances in γδ T Cell-Based Tumor Immunotherapy. Front Immunol. 2017 Oct 27;8:1401.
- 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.
- 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.
- 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.