The Hemopurifier Device for Targeted Removal of Breast Cancer Exosomes from the Blood Circulation

用于从血液循环中靶向去除乳腺癌外泌体的血液净化器装置

基本信息

批准号：
9620493
负责人：
Annette Marleau
金额：
$ 29.84万
依托单位：
AETHLON MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9620493
关键词：
Achievement Address Affinity Agglutinins Blood Blood Circulation Breast Cancer Cell Breast Cancer Patient Breast Cancer Treatment Breast Cancer cell line CSPG4 gene Cancer Patient Cell Culture Techniques Cells Clinical Clinical Trials Development Device Designs Devices Disease ERBB2 gene Evaluation Excision FDA approved Feasibility Studies Flow Cytometry Galanthus nivalis Goals Hematopoietic Neoplasms Hemodialysis Hemofiltration Hour Human Immune Immunophenotyping Immunosuppression Individual Laboratories Lectin Life Lymphocyte Malignant - descriptor Malignant Neoplasms Mediating Medical Device Methods Modeling Molecular Sieve Chromatography Natural Killer Cells Neoplasm Metastasis Non-Malignant Oncogenic Oncoproteins Parents Pathway interactions Patients Pharmaceutical Preparations Phase Phenotype Plasma Plasmapheresis Population Protocols documentation Research Research Support Role SLEB2 gene Stromal Cells Stromal Neoplasm Surface Survival Rate T-Lymphocyte TNFSF10 gene Testing Therapeutic Therapeutic Monoclonal Antibodies Tissues Treatment Protocols Tumor-Derived Universities Ursidae Family Validation Vesicle Virus base chemotherapeutic agent design exosome experimental study glycosylation immune function improved insight interest magnetic beads malignant breast neoplasm nanosized nanovesicle neoplastic cell oncology overexpression prospective research study standard of care success targeted treatment therapy resistant tumor tumor growth

项目摘要

ABSTRACT An overarching challenge in breast cancer oncology is the urgency to revolutionize treatment regimens by replacing them with ones that are more effective, less toxic, and improve the rates of survival. Recent years have seen exponential interest in tumor-derived exosomes; nano-sized (30-150 nm) vesicles shed in large quantities by tumor cells and laden with oncogenic cargo from their parent tumor cell. Research studies have shown that breast cancer cells produce copious quantities of exosomes that are released systemically and mediate tumor- associated immune suppression, resistance to therapies, tissue invasion, and metastasis. Breast cancer exosomes express oncoproteins on their surfaces that have been shown to exert direct actions in interfering with the activity of therapeutic monoclonal antibodies, and countering chemotherapeutic agents. These lines of evidence strongly support the development of strategies to limit the effects of tumor-derived exosomes, however, no such targeted therapeutic strategy exists. The proposed research entails an ex vivo evaluation of a medical device, the Hemopurifier, as a strategy for the capture and removal of exosomes from the plasma of breast cancer patients. The clinical-grade Hemopurifier comprises an extracorporeal hemodialysis cartridge containing a lectin (Galanthus nivalis agglutinin; GNA) affinity matrix. Aethlon has successfully completed an FDA-approved feasibility study using the Hemopurifier for addressing infectious viruses, which have similar sizes and glycosylation signatures as cancer exosomes. Aethlon has also received an Expedited Access Pathway (EAP) designation from the FDA to support the advancement of the Hemopurifier to treat life-threatening viruses. For this prospective new indication for use of the device, our central hypothesis is that the Hemopurifier can be used to target breast cancer exosomes by capturing and removing these vesicles from plasma. In this study, exosomes originating from triple negative and HER2-overexpressing breast cancer cells will be used as a model since research studies have defined the functions of these vesicles in immunosuppression and promoting tumor growth. The proposed proof of concept studies will provide insight into whether exosomes targeted by the Hemopurifier possess signatures and functions that are disease-relevant. We envision that an extracorporeal approach for removing disease-mediating exosomes from circulation may replace or reduce the need for toxic drugs or unmask their efficacy, conceivably serving as an adjunct to standard of care breast cancer treatments.

抽象的乳腺癌肿瘤学的总体挑战是彻底改变治疗方案的紧迫性用更有效，毒性较小并提高生存率的替代它们。近年来有看到对肿瘤衍生的外泌体的指数兴趣；纳米尺寸（30-150 nm）囊泡大量散开通过肿瘤细胞，并从其父肿瘤细胞中载有致癌货物。研究表明乳腺癌细胞会产生大量的外泌体，这些外泌体被系统释放并介导肿瘤 - 相关的免疫抑制，对疗法的抗性，组织侵袭和转移。乳腺癌外泌体在其表面上表达癌蛋白，这些表面已被证明在干扰时会采取直接的作用治疗性单克隆抗体的活性以及对抗化学治疗剂的活性。这些线但是，证据强烈支持制定限制肿瘤衍生外泌体影响的策略没有这种有针对性的治疗策略。拟议的研究需要对医学进行离体评估设备，肢体振荡剂，作为从乳房血浆中捕获和去除外泌体的策略癌症患者。临床级别的临床疗法包括一个含有体外血液透析弹药筒凝集素（Galanthus nivalis凝集素； GNA）亲和力基质。 Aethlon成功完成了FDA批准的可行性研究使用炎症剂来解决具有相似大小和的传染病病毒糖基化特征作为癌症外泌体。 Aethlon还收到了加急访问途径（EAP） FDA的指定为支持血液振荡器的进步以治疗威胁生命的病毒。为了我们使用该设备的前瞻性新指示，我们的中心假设是可以使用肢体疗法通过从血浆中捕获和去除这些囊泡来靶向乳腺癌外泌体。在这项研究中，源自三重阴性和过表达HER2的乳腺癌细胞的外泌体将用作模型由于研究定义了这些囊泡在免疫抑制和促进肿瘤中的功能生长。拟议的概念研究证明将提供有关是否针对的外泌体血液纤维具有与疾病相关的特征和功能。我们设想一个体外从循环中去除疾病的外泌体的方法可能会替代或减少对有毒的需求药物或揭露其功效，可以想象是护理乳腺癌治疗标准的辅助手段。