Nicolás-Morales María Lilia, Luna-Pineda Víctor Manuel, Serrano-Bello Carlos Alberto, Guerrero-Macedonio Miguel David, Rodríguez-Nava Cynthia, Parra-Rojas Isela, Espinoza-Rojo Mónica, Flores-Alfaro Eugenia, Del Carmen Alarcón-Romero Luz, Vences-Velázquez Amalia, Cortés-Sarabia Karen
Laboratorio de Investigación en Inmunobiología y Diagnóstico Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, 39000, Chilpancingo de los Bravo, Guerrero, Mexico.
Hospital Infantil De México Federico Gómez, Doctores, Cuauhtémoc, 06720, Mexico, Mexico.
Sci Rep. 2025 Sep 1;15(1):32134. doi: 10.1038/s41598-025-17914-1.
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 × 10 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.
乳腺癌仍然是全球癌症相关死亡的主要原因，其中三阴性乳腺癌（TNBC）亚型的死亡率特别高。传统免疫疗法已被证明对该亚型无效，这凸显了识别新的肿瘤抗原（如Syntenin-1）的必要性。这种32 kDa的蛋白质与细胞增殖、血管生成和转移有关。最近的研究提出主动免疫疗法（疫苗）和被动免疫疗法（抗体）作为乳腺癌潜在的辅助治疗方法。本研究的主要目的是评估通过主动免疫和被动免疫靶向Syntenin-1作为开发TNBC新免疫疗法策略的疗效。我们进行了计算机分析，以选择一种源自Syntenin-1氨基酸序列的肽，该肽经化学合成作为MAP8。将该肽给予Balb/c小鼠以诱导体液免疫反应。然后使用免疫小鼠获得多克隆抗体以评估主动免疫。总共28只Balb/c小鼠被分为7个实验组。在第3至7组中，通过给予4T1细胞系（5×10个细胞）30天来诱导肿瘤。在肿瘤诱导后的第8、15和22天，以低剂量（1 mg/kg）和高剂量（1 mg/kg）进行被动治疗。处死小鼠以收集血液和器官，用于分析肿瘤生长、转移和体液免疫反应。源自Syntenin-1的PDZ-2结构域的KA-11-MAP8肽在给药后成功诱导Balb/c小鼠产生抗体。纯化的抗体能够识别4T1细胞系和大脑中的天然蛋白质。靶向Syntenin-1的被动和主动治疗均导致肿瘤大小减小和肺部转移结节减少。本研究为源自Syntenin-1的KA-11-MAP8肽在引发体液免疫反应方面的疗效提供了证据，这反过来又影响了TNBC小鼠模型中的肿瘤发展和转移。
