Lefitolimod

Lefitolimod (MGN 1703) is a DNA-based TLR9 agonist and an immune surveillance reactivator. Lefitolimod induces HIV-specific immune responses and can be used for the research of cancer and HIV-1[1][4].

Signaling Pathways >> Immunology/Inflammation >> Toll-like Receptor (TLR)

Research Areas >> Cancer

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

TLR9

HIV-1

Lefitolimod (MGN 1703) might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease[1]. Lefitolimod targets TLR9-positive pDCs and triggers their secretion of IFN-α to activate the effector cells of innate immunity subsequently leading to an elevated systemic level of IP-10, a chemotactic and angiostatic protein[2]. Lefitolimod (MGN1703) (1 μM; 48 h) stimulates cytokine secretion (interferon (IFN)-α, IFN-γ, interleukin (IL)-12, IL-6, and IL-2) and activates immune cells by increased expression of CD80, CD40, human leukocyte antigen (HLA)-DR and ICAM-1[3].

Lefitolimod (MGN1703) (2.5 and 60 μg/day; i.p.; daily for 7 days) raises IL-12p40 levels in mice sera without toxicity[3]. Animal Model: Female C57BL6 mice[3] Dosage: 2.5 and 60 μg/day Administration: Intraperitoneal injection, once daily for 7 days Result: Were able to raise IL-12p40 levels in mice sera.

[1]. Thomas M, et al. Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study. Ann Oncol. 2018 Oct 1;29(10):2076-2084.  

[2]. Jin Y, et al. Development of CpG oligodeoxynucleotide TLR9 agonists in anti-cancer therapy. Expert Rev Anticancer Ther. 2021 Aug;21(8):841-851.  

[3]. Schmidt M, et al. Design and Structural Requirements of the Potent and Safe TLR-9 Agonistic Immunomodulator MGN1703. Nucleic Acid Ther. 2015 Jun;25(3):130-40.  

[4]. McWhirter SM, et al. Nucleic Acid Sensors as Therapeutic Targets for Human Disease. Immunity. 2020 Jul 14;53(1):78-97.