Enhanced lymphokine-activated killer cell activity by an immunomodulator, Roquinimex

Vaz, Fátima; Silva, M. R. G.; Ascensāo, Joāo L.

doi:10.1038/bjc.1995.536

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…Laquinimod (LAQ) is a derivative of linomide (also known as roquinimex). Linomide has immunomodulatory, antiangiogenic, and antineoplastic activity, and was once proposed as a therapy for cancer and autoimmune diseases because it can both enhance and curb immune responses [1,2,3]. Early clinical trials, however, demonstrated considerable toxic effects and were halted [4].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Impact of IMA-08401, a Novel AHR Agonist Resembling Laquinimod, on Rat Liver

Prokopec

Pohjanvirta

Mahiout

et al. 2019

IJMS

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IMA-08401 (C2) is a novel aryl hydrocarbon receptor (AHR) agonist and selective AHR modulator (SAHRM) that is structurally similar to laquinimod (LAQ). Both compounds are converted to the AHR-active metabolite DELAQ (IMA-06201) in vivo. SAHRMs have been proposed as therapeutic options for various autoimmune disorders. Clinical trials on LAQ have not reported any significant toxic outcomes and C2 has shown low toxicity in rats; however, their functional resemblance to the highly toxic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) raises questions. Here, we characterize the hepatic transcriptomic changes induced by acute (single-dose) and subacute exposure (repeated dosing for 5 days followed by a 5-day recovery period) to C2 in Sprague-Dawley rats. Exposure to C2 leads to activation of the AHR, as shown by altered transcription of Cyp1a1. We identify a heightened response early after exposure that drops off by day 10. Acute exposure to C2 leads to changes to transcription of genes involved in antiviral and antibacterial responses, which highlights the immunomodulator effects of this AHR agonist. Subacute exposure causes an oxidative stress response in the liver, the consequences of which require further study on target tissues such as the CNS and immune system, both of which may be compromised in this patient population.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic Impact of IMA-08401, a Novel AHR Agonist Resembling Laquinimod, on Rat Liver

Prokopec

Pohjanvirta

Mahiout

et al. 2019

IJMS

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“…The idea of NK cells as direct target of LAQ treatment is supported by a published study investigating its precursor substance roquinimex. In this work, human adherent lymphokine activated killer cells displayed increased cytotoxicity against NK cell-sensitive K562 tumor cells upon in vitro treatment with roquinimex (Vaz et al, 1995).…”

Section: Laq Treatment Directly Induced Nk Cell Activationmentioning

confidence: 83%

Analyzing the effects of laquinimod on innate and adaptive immunity in mice with experimental autoimmune encephalomyelitis

Ott¹

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Promising Approaches in Acute Leukemia

Cortés

Kantarjian

2000

Invest New Drugs

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In the last few decades, there has been a significant improvement in the prognosis of patients with acute leukemias. Still, the majority of patients succumb to these diseases. In recent years there has been a great surge in the understanding of the molecular mechanisms of disease which have provided us with new targets for anti-leukemia therapy. These range from chemotherapeutic agents with novel mechanisms of action, such as topoisomerase I inhibitors or demethylating agents, to reversal of drug-resistance mechanisms, to monoclonal antibodies directed against specific antigens, and targeted therapy that inhibit the function of molecules such as tyrosine kinases or Ras. The research on many of these agents is still in the early phases, but these new approaches offer the promise of finding a cure for the majority of patients with leukemia in the near future. Here we describe some of the promising approaches that are currently being investigated in the treatment of acute leukemias.

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Enhanced lymphokine-activated killer cell activity by an immunomodulator, Roquinimex

Cited by 3 publications

References 23 publications

Transcriptomic Impact of IMA-08401, a Novel AHR Agonist Resembling Laquinimod, on Rat Liver

Transcriptomic Impact of IMA-08401, a Novel AHR Agonist Resembling Laquinimod, on Rat Liver

Analyzing the effects of laquinimod on innate and adaptive immunity in mice with experimental autoimmune encephalomyelitis

Promising Approaches in Acute Leukemia

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