Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative

Matsumoto, N.; Aze, Yoshiya; Akimoto, Akira; Fujita, Tsuneo

doi:10.1016/s0162-3109(96)00161-0

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…Finally, ONO-4007 is a tri-acylated acyclic sulphonated backbone developed by the Company ONO. Initially, the molecule revealed evidence of antitumor properties in experimental animals [115,116], however promising results were not obtained in phase I clinical studies [116]. On the other hand, although clinical studies have not been developed, ONO-4007 exhibits anti-leishmanial activity [117] and is considered as adjuvant for anti-leishmanial vaccine formulations under co-administration with Leishmanial antigens [118].…”

Section: Synthesis Of Lipid a Analogousmentioning

confidence: 99%

The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

Arenas

2012

EMIDDT

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Bacterial lipopolysaccharide (LPS, endotoxin) is the major constituent of the outer membrane of Gram-negative bacteria. LPS can cause a variety of immune- and cellular disorders that lead to lethal effects and clinical manifestations of infectious diseases. Several molecular and cellular in vitro techniques, besides synthesis of analogous molecules of the LPS active region, have provided insight in the molecular mechanisms of LPS bioactivity in cellular systems. These advances have facilitated the application of diverse LPS-based molecules in relevant areas such as vaccine technology, allergen immunotherapy, treatment of immune-related diseases/disorders, LPS-related inflammatory processes and sepsis. The purpose of this review is to examine the progress in the generation of new LPS-based molecules and their therapeutic potential.

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Section: Synthesis Of Lipid a Analogousmentioning

confidence: 99%

The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

Arenas

2012

EMIDDT

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Section: Cytokinesmentioning

confidence: 99%

“…The lipid A ONO-4007 is mitogenic to spleen cells from BALB/c mice. (16) However, the antitumoral activity of several lipids A in mice was not correlated with mitogenicity for splenocytes, (6) while the lipid A analog GLA-27 reduced melanoma metastasis in mice via NK (natural killer) cell activation. (54) Mechanisms of lipid A antitumoral effects in patients Assays of treatments with pharmaceutical compounds in humans begin with phase I trials aimed at determining the toxicity of potential drugs.…”

Section: Cytokinesmentioning

confidence: 99%

“…(15) Furthermore ONO-4007 injected i.v. slowed the growth of tumors by increasing TNF-a secretion in mice and hamsters (12,16,41) and its efficacy was limited to TNF-a-sensitive tumors in rats, (22,23) but injections of TNF-a itself did not reproduce this effect. (18) The requirement of interferon-(IFN)-g in LPS-induced tumor regression was established in vivo by Dighe et al (42) It was later determined that, during the course of treatment with the bacterial product OM-163 (OM Pharma), the expression of IFN-g mRNA increased in the tumors.…”

Section: Cytokinesmentioning

confidence: 99%

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Mechanisms of the antitumoral effect of lipid A

2002

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Bacterial lipopolysaccharide (LPS) and its active component, lipid A, have been used either alone or as adjuvant in therapeutic anticancer vaccines. Lipid A induces various transcription factors via intracellular signaling cascades initiated by their receptor CD14-TLR4. These events lead to the synthesis of cytokines, which either have direct cytotoxic effect or stimulate the immune system. Their antitumoral effect has been demonstrated in animal models as well as clinical trials. Studies in animal models showed that their antitumoral effect relies mostly on the generation of an effective immune response. In humans, the antitumoral effect was correlatedwith an antibody response and cell-mediated cytotoxicity. So far, some encouraging results have been achieved in phase I and II clinical trials with regards to response and stabilization of the disease, but an expansion of the studies and trials is needed to find the best conditions for their clinical application.

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“…In the present study, we evaluated whether or not oral administration of a cell preparation of E. faecalis strain KH-2 (CPEF) stimulated cell-mediated immunity such as NK activity in a mouse model. We further aimed to test whether or not oral administration of CPEF was effective for preventing tumour development using Meth-A fibrosarcoma-bearing mice, which represent an in vivo screening model commonly used to evaluate the antitumour activity of functional foods or alternative medicines [ 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of murine cell-mediated immunity by dietary administration of a cell preparation of <i>Enterococcus faecalis</i> strain KH-2 and its possible activity against tumour development in mice

Tsukahara

Nakamura

Romero-Pérez

et al. 2018

Bioscience of Microbiota, Food and Health

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It is well known that dietary lactic acid bacteria (LAB) stimulate cell-mediated immunity such as natural killer (NK) activity in mice. Here, we aimed to assay the immunomodulatory effects of a cell preparation of Enterococcus faecalis strain KH-2 (CPEF). We further evaluated the possibility of antitumour activity caused by CPEF administration, because NK cells actively participate in the prevention of tumour formation. NK cell activity and gene expression of IFN-γ and Perforin 1, which were induced most likely by a synergetic action of their cytotoxic activity, were higher in splenocytes of CPEF-administered mice than they were in control mice. Moreover, unlike those of control mice, the splenocytes of CPEF-administered mice had significantly higher CD28+CD69+/CD4+ and CD28+CD69+/CD8+ ratios that resulted in a survival rate with a tendency toward improvement after 47 days of CPEF administration (p=0.1) in Meth-A fibrosarcoma-bearing mice. In conclusion, we showed that CPEF might be effective in treating Meth-A fibrosarcoma in mice, as it helped increase their survival rate via stimulation of an immune response in splenocytes, which involved systemic cellular immunity processes such as cytotoxic activity, and active T cells.

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Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative

Cited by 11 publications

References 31 publications

The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

Mechanisms of the antitumoral effect of lipid A

Stimulation of murine cell-mediated immunity by dietary administration of a cell preparation of <i>Enterococcus faecalis</i> strain KH-2 and its possible activity against tumour development in mice

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