Cecil Denise L, Herendeen Daniel, Slota Meredith, O'Meara Megan M, Dang Yushe, Corulli Lauren, Disis Mary L
Cancer Vaccine Institute, University of Washington, Seattle, WA 98109, USA.
Vaccines (Basel). 2025 May 15;13(5):525. doi: 10.3390/vaccines13050525.
Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a promising therapeutic approach.
Twelve candidate CSC/EMT-associated proteins were identified through a systematic literature review. Human serum samples were assessed for antigen-specific IgG using ELISA. Th1/Th2 cytokine profiles, in response to predicted MHC II epitopes, were measured by ELISPOT in PBMCs. Epitope immunogenicity and tumor inhibition were evaluated in murine models, using either TNBC or luminal B syngeneic breast cancer cell lines.
Six of the candidate proteins (SOX2, YB1, FOXQ1, MDM2, CDH3, CD105) elicited antigen-specific IgG in human serum. Th1-selective epitopes, defined by high Th1/Th2 ratios, were identified for five of these proteins. Immunization of mice with peptide pools derived from CD105, CDH3, MDM2, SOX2, and YB1 induced significant antigen-specific IFN-γ responses. Tumor growth was significantly inhibited in the vaccinated mice across both the TNBC and luminal B breast cancer models, with mean tumor volume reductions ranging from 61% to 70%.
CSC/EMT-associated antigens are immunogenic in humans and can be targeted using Th1-selective epitope-based vaccines. Immunization with these epitopes effectively inhibits tumor growth in multiple murine models of breast cancer. These findings support further clinical evaluation of CSC/EMT-targeted vaccines, especially for high-risk or advanced-stage breast cancer patients.
乳腺癌干细胞（CSCs），尤其是那些在三阴性乳腺癌（TNBC）中富集的干细胞，是肿瘤复发、转移和治疗抵抗的关键因素。CSCs常经历上皮-间质转化（EMT），增强其侵袭性。选择性靶向CSC/EMT抗原的免疫策略提供了一种有前景的治疗方法。
通过系统的文献综述确定了12种候选CSC/EMT相关蛋白。使用酶联免疫吸附测定（ELISA）评估人血清样本中的抗原特异性IgG。通过酶联免疫斑点法（ELISPOT）在外周血单核细胞（PBMCs）中测量对预测的MHC II表位的Th1/Th2细胞因子谱。使用TNBC或腔面B同基因乳腺癌细胞系在小鼠模型中评估表位免疫原性和肿瘤抑制作用。
六种候选蛋白（SOX2、YB1、FOXQ1、MDM2、CDH3、CD105）在人血清中引发了抗原特异性IgG。为其中五种蛋白确定了由高Th1/Th2比值定义的Th1选择性表位。用源自CD105、CDH3、MDM2、SOX2和YB1的肽池免疫小鼠诱导了显著的抗原特异性干扰素-γ反应。在TNBC和腔面B乳腺癌模型中，接种疫苗的小鼠肿瘤生长均受到显著抑制，平均肿瘤体积减少61%至70%。
CSC/EMT相关抗原在人类中具有免疫原性，可使用基于Th1选择性表位的疫苗进行靶向。用这些表位免疫可有效抑制多种乳腺癌小鼠模型中的肿瘤生长。这些发现支持对CSC/EMT靶向疫苗进行进一步的临床评估，特别是针对高危或晚期乳腺癌患者。
