Effects of Hu-Mikβ1, Raltegravir, and Mogamulizumab on Immune Activation and Motor Function in HAM/TSP
Year: 2025
Type: article
Abstract: Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes chronic neuroinflammation, leading to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is characterized by motor disability and overactivation of immune cells. There are currently no therapies that effectively halt disease progression. We evaluated three targeted interventions: Hu-Mikβ1, a humanized monoclonal antibody that blocks the IL-2/IL-15 receptor β chain (CD122) to reduce overactive T cell and NK cell signaling; raltegravir, an integrase inhibitor that limits viral replication and secondary immune activation; and mogamulizumab, an anti-CCR4 antibody that depletes infected T cells. Hu-Mikβ1 reduced circulating CD56+ natural killer (NK) cells and decreased CD8+ T cell cytotoxicity, as shown by lower CD107a, IFN-γ, and phosphorylated STAT5 (pSTAT5) levels. Raltegravir decreased activated CD8+ CD122+ T cells in peripheral blood but had limited effects in cerebrospinal fluid (CSF). Mogamulizumab lowered proviral load (64.9% by day 15) and CSF neopterin (45.1% by week 24), improving spasticity and motor function in 79% of patients. These results highlight the potential of targeting CD122, viral replication, and CCR4+ T cells and provide data for future combination therapies to reduce immune-mediated neurodegeneration in HAM/TSP.
DOI: 10.13021/mars/15125
Authors: Wong, Serena, Saad, Sara, Kashanchi, Faith
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7090958653
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