Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells

Zhang, B; Kf, Wu; Ym, Lin; Xt, Ma; Rao, Qing; Zheng, Guoguang; Zy, Cao; G, Li; Song, Yafeng

doi:10.1038/sj.leu.2403320

Cited by 14 publications

(6 citation statements)

References 47 publications

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“…IL-18 is a useful candidate gene in gene therapy of lymphoma or lymphoid leukemia. (Zhang et al, 2004). The combination of IL-18 and IL-2 is considered a viable strategy to induce an antitumor response in vivo (Young et al, 2001).…”

Section: Immuno Therapeuticsmentioning

confidence: 99%

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala¹,

Syed²,

Bandaru³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

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Section: Immuno Therapeuticsmentioning

confidence: 99%

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala¹,

Syed²,

Bandaru³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…A crucial role for T cell immunity has been proposed for the control of leukemic malignancies. Interestingly, an IL-18 gene transfer approach showed promising results in a murine model of lymphoid leukemia (45).…”

Section: Il-18 -Induced T-bet In Kg-1 Cellsmentioning

confidence: 99%

Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-κB in acute myeloid leukemia–derived predendritic KG-1 cells

Bachmann

Drăgoi

Poleganov

et al. 2007

Molecular Cancer Therapeutics

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The leukemic cell line KG-1 was isolated from a patient with acute myeloid leukemia and is regarded a cellular model of human dendritic cell progenitors. The T helper type 1 cytokine interleukin (IL)-18 has been shown to induce the maturation of these cells towards a dendritic phenotype and, moreover, is able to mediate IFN; production in this model. Because T-box expressed in T cells (T-bet) is considered to be of paramount importance for dendritic cell function, the effects of IL-18 on this transcription factor have been investigated in the current study. Here, we show that activation of KG-1 cells by IL-18 induces T-bet mRNA and protein within 4 to 6 h of incubation. This hitherto unrecognized function of IL-18 was suppressed by the inhibition of p38 mitogen-activated protein kinase activity and nuclear factor-KB function.

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“…Immunotherapy with acute leukemia cells modified to express immunomodulators is a promising approach for the treatment of leukemia (14)(15)(16)(17)(18)(19)(20)(21)(22). Many leukemic cells are easy to harvest for manipulation.…”

Section: Introductionmentioning

confidence: 99%

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

et al. 2006

Cancer Research

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Murine B-defensin 2 (MBD2) is a small antimicrobial peptide of the innate immune system. Recent study showed that MBD2 could not only recruit immature dendritic cells but also activate them by Toll-like receptor 4 and thus may provide a critical link between the innate immune system and the adaptive immune response. In this report, we examined the antileukemia activity of MBD2 in a murine model of acute lymphoid leukemia (ALL) L1210. L1210 cells were engineered to secrete biologically functional MBD2. MBD2-modified L1210 (L1210-MBD2) showed significantly reduced leukemogenecity, resulting in a 80% rate of complete leukemia rejection. Inoculation of mice with L1210-MBD2 induced enhanced CTL and natural killer (NK) activity and augmented interleukin-12 and IFN-; production. All the recovered mice from the inoculation showed a protective immunity to the following challenge with parental L1210 cells and generate leukemia-specific memory CTL. Vaccines with irradiated L1210-MBD2 cells could cure 50% leukemia-bearing mice. Depletion of CD8 + T cells but not CD4 + T cells completely abrogated the antileukemia activity of MBD2. Interestingly, NK cells were also required for the MBD2-mediated antileukemia response, although ALL generally display a high degree of resistance to NK-mediated lysis. Our results suggest that MBD2 can activate both innate and adaptive immunity to generate potent antileukemia response, and MBD2 immunotherapy warrants further evaluation as a potential treatment for ALL. (Cancer Res 2006; 66(2): 1169-76)

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Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells

Cited by 14 publications

References 47 publications

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-κB in acute myeloid leukemia–derived predendritic KG-1 cells

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

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