Cobomarsen (MRG-106) is an oligonucleotide inhibitor targeting miR-155 that effectively suppresses gene pathways involved in cell survival, including JAK/STAT, MAPK/ERK, and PI3K/AKT, and is particularly valuable in the study of B-cell lymphoma.

Cobomarsen, at a concentration of 10 μM and exposure durations ranging from 48 to 96 hours, effectively hampers cell proliferation and triggers apoptosis in U2932, OCI-LY3, and RCK8 cell lines. Furthermore, a 72-hour exposure to the same concentration markedly enhances the expression of miR-155's four direct targets within cell lines that exhibit miR-155 overexpression. Over a 12-day treatment period, Cobomarsen also significantly deters cellular proliferation and promotes apoptosis in Mycosis Fungoides (MF) and Human T-lymphotropic Virus 1 positive (HTLV-1+) Cutaneous T-cell Lymphoma (CTCL) cells. Additionally, a 7-day application of Cobomarsen, ranging from 10 to 50 μM, diminishes phosphorylation levels of key downstream signaling proteins, namely AKT, ERK1/2, and STAT-3, in primary activated human T cells or MF cell lines. Assays conducted on cell proliferation and apoptosis across U2932, OCI-LY3, and RCK8 cells with a consistent 10 μM concentration of Cobomarsen showcased a dose-dependent reduction in cell phosphorylation and a significant enhancement in late-stage apoptosis across all examined cell lines.

Cobomarsen (1 mg/kg; i.v. on days 0, 2, 4, and 7) significantly reduces tumor growth in five-to-six-week-old female NSG mice implanted with U2932 cell xenografts, with the most notable reduction on days 7 and 10, demonstrating its efficacy in this animal model[2].