Department of Animal Medicine, Surgery and Pathology, Mammary Oncology Unit, Veterinary Teaching Hospital, Veterinary Medicine School, Complutense University of Madrid, 28040 Madrid, Spain.
Institute of Laboratory Animal Science, University of Zurich, 8952 Schlieren, Switzerland.
Cells. 2023 Sep 8;12(18):2241. doi: 10.3390/cells12182241.
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.
缺乏评估新型药物的最佳模型，阻碍了针对人乳腺癌（BC）的有效免疫疗法的发展。在这项前瞻性开放标签研究中，我们对 11 只被诊断患有犬乳腺肿瘤（CMC）的伴侣犬应用了载空豇豆花叶病毒样颗粒（eCPMV）的新辅助瘤内免疫疗法，CMC 是一种类似于人 BC 的自发性肿瘤。我们发现，在所有患者中，两次新辅助瘤内 eCPMV 注射可导致注射肿瘤和注射犬同侧和对侧乳腺链中的未注射肿瘤缩小。肿瘤缩小与临床分期、肿瘤大小、组织病理学分级和肿瘤分子亚型无关。注射肿瘤的 RNA-seq 分析表明，肿瘤微环境中的 DNA 复制活性降低，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、T 和 B 淋巴细胞以及浆细胞显著增加。eCPMV 瘤内免疫疗法具有抗肿瘤疗效，无任何不良反应。这种新型免疫疗法有可能改善人 BC 患者的预后。
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