Tumor nano-lysate activates dendritic cells to evoke a preventative immune response

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Jenna A. Dombroski , Abigail R. Fabiano , Samantha V. Knoblauch , Schyler J. Rowland , Katherine N. Gibson-Corley , Michael R. King
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Abstract

A tumor nano-lysate “TNL” vaccine comprised of sonicated 4T1 cells was developed, characterized and implemented for the prevention of triple-negative breast cancer. This study aimed to gain a better understanding of the immune response behind the success of the vaccine in vivo, through use of ex vivo and in vivo assays. Here, we analyze the activation of various immune cells isolated from healthy mouse spleens and find that antigen-presenting cells (APCs) such as dendritic cells (DCs) are being activated following 24 h incubation with 1:10 mg TNL/mg splenocytes. These cells were further explored to determine the pathway by which activation is occurring, and it was observed that TNL are phagocytosed by DCs to activate NF-kB and c-Fos pathways, resulting in enhanced cytokine release after 24 h. An in vivo temporal analysis was performed in mice to understand the immune response at 1, 3, 7 and 10 days after one 100 μL dose of TNL consisting of 105 sonicated 4T1 cells via cardiac puncture and splenocyte and peripheral blood mononuclear cell (PBMC) analysis. Changes were observed for up to one week. A multiple dose study was performed comparing mice that were vaccinated with one dose of TNL administered every ten days for 3 doses total, as well as a PBS vehicle control. Survival for TNL-vaccinated mice was enhanced compared to the PBS control, and there was an average delay of 10 days in the onset of metastasis. The differences between the groups at the end of the study demonstrate the potential for TNL as a preventative therapeutic.

肿瘤纳米溶液激活树突状细胞,唤起预防性免疫反应
为预防三阴性乳腺癌,我们开发了一种由超声 4 T1 细胞组成的肿瘤纳米溶液 "TNL "疫苗,并对其进行了表征和实施。本研究旨在通过使用体内外试验,更好地了解该疫苗在体内取得成功背后的免疫反应。在这里,我们分析了从健康小鼠脾脏中分离出的各种免疫细胞的活化情况,发现树突状细胞(DC)等抗原递呈细胞(APC)在与 1:10 毫克 TNL/mg 脾细胞培养 24 小时后被激活。我们对这些细胞进行了进一步研究,以确定发生活化的途径,结果发现 TNL 被 DC 吞噬后激活了 NF-kB 和 c-Fos 通路,导致 24 小时后细胞因子释放增加。通过心脏穿刺和脾脏细胞及外周血单核细胞(PBMC)分析,对小鼠进行了体内时间分析,以了解小鼠在服用由 105 个超声 4 T1 细胞组成的 100 μL 剂量 TNL 后 1、3、7 和 10 天的免疫反应。观察变化长达一周。对每十天接种一剂 TNL 共 3 剂的小鼠和 PBS 药物对照进行了多剂量研究比较。与 PBS 对照组相比,接种 TNL 疫苗的小鼠存活率更高,转移的发生平均推迟了 10 天。研究结束时各组之间的差异证明了 TNL 作为一种预防性疗法的潜力。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
120
审稿时长
3 months
期刊介绍: The Journal of Immunological Methods is devoted to covering techniques for: (1) Quantitating and detecting antibodies and/or antigens. (2) Purifying immunoglobulins, lymphokines and other molecules of the immune system. (3) Isolating antigens and other substances important in immunological processes. (4) Labelling antigens and antibodies. (5) Localizing antigens and/or antibodies in tissues and cells. (6) Detecting, and fractionating immunocompetent cells. (7) Assaying for cellular immunity. (8) Documenting cell-cell interactions. (9) Initiating immunity and unresponsiveness. (10) Transplanting tissues. (11) Studying items closely related to immunity such as complement, reticuloendothelial system and others. (12) Molecular techniques for studying immune cells and their receptors. (13) Imaging of the immune system. (14) Methods for production or their fragments in eukaryotic and prokaryotic cells. In addition the journal will publish articles on novel methods for analysing the organization, structure and expression of genes for immunologically important molecules such as immunoglobulins, T cell receptors and accessory molecules involved in antigen recognition, processing and presentation. Submitted full length manuscripts should describe new methods of broad applicability to immunology and not simply the application of an established method to a particular substance - although papers describing such applications may be considered for publication as a short Technical Note. Review articles will also be published by the Journal of Immunological Methods. In general these manuscripts are by solicitation however anyone interested in submitting a review can contact the Reviews Editor and provide an outline of the proposed review.
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