Vidutolimod  (Synonyms: CMP-001)

Vidutolimod (CMP-001) is a virus-like particle containing a TLR9 activator. Vidutolimod induces human peripheral blood mononuclear cells to secrete IFNα, and upregulates the gene expression of CXCL10, PDL1, IDO and CD80. Vidutolimod activates TLR9, which in turn triggers plasmacytoid dendritic cell activation, production of IFNγ and TNFα, induction of CXCL10, and recruitment of antitumor T cells. Vidutolimod causes influenza-like symptoms, hypotension and tumor regression, and its activity depends on the presence of anti-Qβ antibodies. Vidutolimod modulates monocyte function, promotes CD4 T cell proliferation, and activates multiple immune cell types in an environment with anti-Qβ antibodies. Vidutolimod prolongs the survival of tumor-bearing mice. Vidutolimod is used in research related to advanced melanoma, head and neck squamous cell carcinoma, and advanced non-small cell lung cancer^[1][2][3][4].

Vidutolimod (2.5-10 μg/mL; 48 h) potently induces IFNα secretion by normal human peripheral blood mononuclear cells^[2].
Vidutolimod (Anti-Qβ-coated) (10 μg/mL; 24 h) significantly induces the upregulation of interferon response-related genes and immune communication-related genes (including CXCL10, PDL1, IDO, and CD80) in monocytes derived from peripheral blood mononuclear cells (PBMCs) of healthy donors^[3].
Vidutolimod (Anti-Qβ-coated) (10 μg/mL; 24 h) indirectly induces CXCL10 production in monocytes from healthy donors via type I interferons (primarily IFN-β) produced by plasmacytoid dendritic cells (pDCs), and this process does not require intercellular contact between pDCs and monocytes^[3].
Vidutolimod (Anti-Qβ-coated) (10 μg/mL; 24 h) enhances the expression of IDO and PDL1 in monocytes from healthy donors. The induction of IDO depends on the type I IFN signaling pathway mediated by IFNAR2, while the induction of PDL1 may involve other non-IFN-dependent factors^[3].
Vidutolimod (Anti-Qβ-coated) (10 μg/mL; 1 h uptake assay, 18-20 h phenotype analysis) regulates the IFN-α-induced responses of PDL1 and CXCL10 in monocytes from healthy donors in a CD32a-mediated phagocytosis-dependent manner, while the regulation of IDO also involves other Fc receptor signaling pathways (e.g., CD64)^[3].
Treatment with Vidutolimod (Anti-Qβ-coated) (10 μg/mL; 18-20 h) and IFN-α upregulates CD80 expression on monocytes from healthy donors and enhances their capacity to induce the proliferation of autologous CD4⁺ T cells^[3].
Combination of vidutolimod (5 µg/mL; 24 h) with anti-Qβ activates human plasmacytoid dendritic cells (pDCs) and monocytes^[4].
Combined with anti-Qβ, Vidutolimod (5 µg/mL; 24 h) activates primary human CD4⁺ T cells, CD8⁺ T cells and NK cells, and increases the secretion levels of IFNγ and TNFα in a co-culture system with HPV⁺ UM-SCC47 head and neck squamous cell carcinoma cells^[4].
Combination of Vidutolimod and anti-Qβ directly activates isolated primary human NK cells co-cultured with HPV⁺ UM-SCC47 HNSCC cells, yet this response is weaker than that observed in the co-culture system of intact peripheral blood mononuclear cells (PBMC) in the presence of dendritic cells (DC)^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Vidutolimod (100 µg/mouse; subcutaneous injection; single dose, 2 weeks prior to tumor inoculation; intratumoral injection; 3 doses, on days 14, 17, and 20 post tumor inoculation / on days 11, 15, and 19 post tumor inoculation) enhances its intratumoral anti-tumor activity and survival benefit in mice bearing mEERL head and neck squamous cell carcinoma (HNSCC) tumors, increases immune cell infiltration in tumors and draining lymph nodes, and its anti-tumor effect and survival benefit are dependent on CD8⁺ T cells^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

9612.20

147063-80-7

Solid

White to off-white

DNA, d(G-G-G-G-G-G-G-G-G-G-G-A-C-G-A-T-C-G-T-C-G-G-G-G-G-G-G-G-G-G)

[Vidutolimod]

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Negrao MV, et al. Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade-Resistant Advanced NSCLC. JTO Clin Res Rep. 2022;4(3):100423. Published 2022 Oct 26.  [Content Brief]

  [2]. Ribas A, et al. Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma. Cancer Discov. 2021;11(12):2998-3007.  [Content Brief]

  [3]. Sabree SA, et al. Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist. J Immunother Cancer. 2021;9(6):e002484.  [Content Brief]

  [4]. Cheng Y, et al. In situ immunization of a TLR9 agonist virus-like particle enhances anti-PD1 therapy. J Immunother Cancer. 2020 Oct;8(2):e000940.  [Content Brief]