PDF(Pubmed)
Abstract：
The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.
摘要：
缺乏评估新型药物的最佳模型正在延迟针对人类乳腺癌（BC）的有效免疫疗法的开发。在这项前瞻性开放标签研究中，我们应用新辅助瘤内免疫疗法与空cow豆花叶病毒样颗粒（eCPMV）对11只诊断为犬乳腺癌（CMC）的伴侣犬，类似于人类BC的自发性肿瘤。我们发现，两次新辅助肿瘤内注射eCPMV可导致所有患者的注射肿瘤以及位于注射犬同侧和对侧乳腺链中的非注射肿瘤的肿瘤减少。肿瘤缩小与临床分期无关，肿瘤大小,组织病理学分级,和肿瘤分子亚型。注射肿瘤的基于RNA-seq的分析表明DNA复制活性降低，肿瘤微环境中激活的树突状细胞浸润增加。免疫组织化学分析显示肿瘤内中性粒细胞显著增加，T和B淋巴细胞，和浆细胞。eCPMV肿瘤内免疫治疗显示抗肿瘤疗效，无任何不良反应。这种新型免疫疗法具有改善人类BC患者预后的潜力。
