Work

The therapeutic potential of targeting IL-1α signaling pathways in a mouse model of pulmonary melanoma

Year: 2026

Type: article

Abstract: Interleukin-1α (IL-1α) is a critical mediator of tumor progression and metastasis and has been implicated in the pathogenesis of both benign and malignant melanocytic lesions. In this study, the antitumor efficacy of Flo1-2a, a murine surrogate for the anti-IL-1α monoclonal antibody vilamakitug (also known as Natrunix, XB2001), was assessed using a murine model of pulmonary melanoma metastasis. Mice were inoculated with B16-F10 cells to induce pulmonary nodules, allowing for determination of the optimal Flo1-2a dosage to attenuate nodule burden and metastatic dissemination. Administration of Flo1-2a at 1.0 mg/dose markedly suppressed pulmonary melanoma metastasis, and significantly prolonged long-term survival through IL-1α neutralization. Quantitative PCR analysis of lung tissue from B16-F10-inoculated mice demonstrated that Flo1-2a treatment reduced expression of melanoma-associated genes including MMP2, MMP9, VEGF, PD-L1, and IL-1α, the latter suggesting concurrent disruption of IL-1α autocrine feedback signaling, relative to untreated controls. Immunohistochemical analysis with hematoxylin counterstaining further confirmed lower protein expression and reduced area percentages of MMP9, PD-L1, and IL-1α in Flo1-2a–treated lung tissues. Collectively, these findings identify IL-1α as a key mediator of melanoma lung metastasis. Moreover, we demonstrate that antibody-mediated IL-1α blockade effectively inhibits metastatic progression in this preclinical model, supporting IL-1α-targeted therapy as a promising strategy for metastatic melanoma.

Source: Scientific Reports

DOI: 10.1038/s41598-026-66972-6