通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer.
The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer.
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TIL(肿瘤浸润淋巴细胞)的缺失会对所有亚型乳腺癌的化疗反应和预后产生负面影响。刺激促炎环境的治疗可能有助于改善对标准治疗以及免疫治疗(如检查点抑制剂)的反应。新城疫病毒(NDV)在体外和体内乳腺癌治疗中显示出溶瘤活性以及免疫调节潜力;然而,其增强乳腺癌肿瘤浸润免疫细胞的潜力尚未被评估。由于自发性犬乳腺肿瘤是人类乳腺癌的转化模型,我们开展了这项概念验证研究,这可能为进一步研究 NDV-MLS 作为乳腺肿瘤免疫治疗提供依据。六只患有自发性乳腺肿瘤的雌性伴侣犬接受了单次静脉内和瘤内注射溶瘤 NDV-MLS。在病毒给药后第 6 天,通过组织学和免疫组织化学评估了基质、瘤内和瘤周区域中的免疫细胞浸润。病毒治疗后记录到免疫细胞数量增加,主要在瘤周区域,其中浆细胞以及 CD3+ 和 CD3-/CD79- 淋巴细胞占主导。病毒给药耐受良好,未出现显著不良事件。这些发现支持进一步研究使用 NDV-MLS 免疫治疗乳腺肿瘤。
The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated.
Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS.
Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events.
These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.
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