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纳米球疫苗介导的黑色素瘤免疫疗法引发CD4+和CD8+ T细胞反应以实现肿瘤消退。

Melanoma immunotherapy by nanosphere-vaccine elicited CD4+ and CD8+ T-cell response for tumor regression.

作者信息

Javvaji Kalpana, Vangala Venugopal, Sayana Suresh Babu, Maturi Bhanu, Bhamidipati Keerti, Brunt Keith R, Misra Sunil, Kandimalla Ramesh, Puvvada Nagaprasad

机构信息

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

出版信息

Nanomedicine. 2025 Jun;66:102817. doi: 10.1016/j.nano.2025.102817. Epub 2025 Apr 5.

DOI:10.1016/j.nano.2025.102817
PMID:40194752
Abstract

Melanoma, driven by defective immune surveillance and cancer-cell evasion, has rising morbidity and mortality due to solar radiation exposure and delayed diagnosis. Effective tumor opsonization and phagocytosis are needed, demanding new therapeutic formulations. Here, we demonstrate the efficacy of a novel lipid-coated glucose nanosphere (LGNP) formulation decorated with ovalbumin (OVA) and containing pCMV-MART-1 (MT-1), termed the nLOM vaccine. This vaccine elicits specific immune responses through bone marrow DC maturation and CD4+/CD8+ T-cell activation, targeting melanoma antigens. In preclinical studies using orthotopic B16-F10 melanoma cells in C57BL/6J mice, the vaccine induced significant infiltration of T lymphocytes into tumor tissues, reducing tumor progression. Robust immune responses were observed in the spleens and inguinal lymph nodes of vaccinated mice, characterized by elevated cytokine levels. These findings suggest that the nLOM vaccine could elicit durable immunogenicity against melanoma through enhanced antigen presentation and holds promise for clinical development as an effective immunotherapy.

摘要

黑色素瘤由有缺陷的免疫监视和癌细胞逃逸驱动,因太阳辐射暴露和诊断延迟,其发病率和死亡率不断上升。需要有效的肿瘤调理作用和吞噬作用,这就需要新的治疗制剂。在此,我们展示了一种新型脂质包被的葡萄糖纳米球(LGNP)制剂的疗效,该制剂用卵清蛋白(OVA)修饰并含有pCMV-MART-1(MT-1),称为nLOM疫苗。这种疫苗通过骨髓树突状细胞成熟和CD4+/CD8+ T细胞活化引发特异性免疫反应,靶向黑色素瘤抗原。在使用C57BL/6J小鼠原位B16-F10黑色素瘤细胞的临床前研究中,该疫苗诱导T淋巴细胞大量浸润肿瘤组织,减少肿瘤进展。在接种疫苗的小鼠脾脏和腹股沟淋巴结中观察到强烈的免疫反应,其特征是细胞因子水平升高。这些发现表明,nLOM疫苗可通过增强抗原呈递引发针对黑色素瘤的持久免疫原性,并有望作为一种有效的免疫疗法进行临床开发。

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