The administration of passive and active immunotherapy against Syntenin-1 decreased the tumoral growth and pulmonary metastasis in a murine model of triple-negative breast cancer

Breast cancer remains the leading cause of cancer-related deaths worldwide, with the triple-negative breast cancer (TNBC) subtype exhibiting a particularly high mortality rate. Conventional immunotherapy treatments have proven ineffective for this subtype, highlighting the need for the identification of novel tumor antigens, such as Syntenin-1. This 32 kDa protein is linked to cellular proliferation, angiogenesis, and metastasis. Recent research has proposed both active (vaccines) and passive (antibodies) immunotherapy as potential complementary treatments for breast cancer. The primary objective of this study was to assess the efficacy of targeting Syntenin-1 through active and passive immunity as a strategy for developing new immunotherapies for TNBC. We conducted an in silico analysis to select a peptide derived from the amino acid sequence of Syntenin-1, which was synthesized chemically as MAP8. This peptide was administered to Balb/c mice to induce a humoral immune response. Immunized mice were then used to obtain polyclonal antibodies for evaluating active immunity. A total of twenty-eight Balb/c mice were divided into seven experimental groups. Tumor induction was achieved by administering the 4T1 cell line (5 × 10⁴ cells) for 30 days in groups 3-7. Passive treatment was given at low (1 mg/kg) and high (1 mg/kg) doses on days 8, 15, and 22 following tumor induction. Mice were sacrificed to collect blood and organs for analyzing tumor growth, metastasis, and the humoral immune response. The KA-11-MAP8 peptide, derived from the PDZ-2 domain of Syntenin-1, successfully induced antibody production in Balb/c mice after administration. Purified antibodies were able to recognize the native protein in both the 4T1 cell line and the brain. Both passive and active treatments targeting Syntenin-1 resulted in reduced tumor size and fewer metastatic nodules in the lungs. This study provides evidence for the efficacy of the KA-11-MAP8 peptide derived from Syntenin-1 in eliciting a humoral immune response, which in turn impacts tumor development and metastasis in a murine model of TNBC.