Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

• DOI: 10.1016/j.omto.2022.07.004
• Publication Date: 2022-07-09T04:46:06Z
• Authors: Guillermo Herrado...; Marta Zalacain; Sara Labiano; Virginia Laspidea; Montserrat Puigde...; Lucía Marrodan; Marc Garcia-Moure; Marisol Gonzalez-...; Javier Marco-Sanz; Iker Ausejo-Mauleon; Daniel de la Nava; Reyes Hernández-O...; Javier Martínez-G...; Noelia Silva-Pili...; Elisabeth Gurucega; Ana Patiño-García; Rubén Hernández-A...; Cristian Smerdou; Marta M. Alonso
• Keywords: Semliki Forest virus; Galectin-3; Immunosuppression

The outcomes of metastatic and nonresponder pediatric osteosarcoma patients are very poor have not improved in the last 30 years. These tumors harbor a highly immunosuppressive environment, making existing immunotherapies ineffective. Here, we evaluated use Semliki Forest virus (SFV) vectors expressing galectin-3 (Gal3) inhibitors as therapeutic tools, since both inhibition Gal3, which is involved immunosuppression metastasis, virotherapy based on SFV been demonstrated to reduce tumor progression different models. In vitro, Gal3 amino-terminal domain alone (Gal3-N) or fused peptide inhibitor (Gal3-N-C12) were able block binding surface activated T cells. vivo, Gal3-N-C12 induced strong antitumor responses orthotopic K7M2 MOS-J tumors, leading complete regressions 47% 30% mice, respectively. Pulmonary metastases also reduced tumor-bearing mice after treatment with SFV-Gal3-N-C12. Both antimetastatic dependent modulation immune system, primarily including an increase tumor-infiltrating lymphocytes reduction environment inside tumors. Our results that SFV-Gal3-N-C12 could constitute potential agent for Gal3.