2/2 Pilot Project 1: Langston University-UNTHSC Partnership for Cancer Research and Education

2/2 试点项目 1：兰斯顿大学-UNTHSC 癌症研究和教育合作伙伴关系

• 批准号: 10237231
• 负责人: Harlan Pierre Jones
• 金额: $ 6.14万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237231
• 关键词: Address; Antibodies; Antigens; Antitumor Response; Bacterial Antigens; Breast Cancer Patient; Cancer Etiology; Cancer Vaccines; Cessation of life; Clinical; Cordyceps; Development; Diagnosis; Distal; Encapsulated; Enhancers; Excision; Goals; Health Sciences; Immune; Immune Tolerance; Immune response; Immune system; Immunologic Adjuvants; Immunotherapy; Intervention; Intranasal Administration; Intrinsic factor; Knowledge; Lesion; Light; Literature; Lung; Lung Neoplasms; Malignant Neoplasms; Mediator of activation protein; Metastatic Neoplasm to the Lung; Metastatic breast cancer; Molecular; Mucosal Immunity; Mucous Membrane; Nanotechnology; Neoplasm Metastasis; Nose; Operative Surgical Procedures; Organ; Outcome; Patient-Focused Outcomes; Patients; Pattern; Phenotype; Pilot Projects; Plant Extracts; Primary Neoplasm; Property; Radio; Research; Research Personnel; Resistance; Surface; Survival Rate; System; Technology; Testing; Texas; Therapeutic; Trigonella foenum-graecum; Tumor Antigens; Tumor Escape; Tumor Immunity; Universities; Vaccines; anti-cancer; anti-tumor immune response; anticancer research; antitumor effect; base; cancer education; cancer health disparity; cancer prevention; cancer therapy; chemoradiation; combinatorial; cytokine; design; expectation; immune function; immunoregulation; improved; innovation; malignant breast neoplasm; meetings; metabolomics; nanoparticle; nanoparticle delivery; neoplastic cell; novel; particle; pathogen; preclinical trial; prevent; prophylactic; side effect; tumor; tumor microenvironment

Abstract Approximately 90% of deaths due to breast cancer are from metastatic tumor spread to distal organs. Secondary lung metastases are identified in 30-55% of these patients and unfortunately the 5-year survival rate is only 30-40% for surgical resection and chemo-radio treatments. These poor outcomes signify a critical need to further understand the mechanisms impacting tumor metastasis. The long-term goal of our research is to design innovative approaches that increase the immune system's ability to prevent lung tumor metastasis through an increased knowledge of anti-tumor immunity. Current immune-based strategies that implement soluble cytokines and antibodies have been introduced in clinical and pre-clinical trials to broadly boost immune responses against cancers. However, off-target organ damage and immune tolerance has significantly limited their use. Particle-based nanotechnology is emerging as a feasible approach to manipulate immune function. However, we do not fully understand how these components influence immune phenotype and function as a predictor of tumor cell escape and the efficacy of nanoparticle use could benefit improve immune therapy. Based on previous literature findings and our own preliminary findings described in this application, our central hypotheses are: 1) Intranasal administration of CPG bound to the surface of NP-encapsulated tumor antigen induces protective lung mucosal immune protection against secondary lung tumor metastases and 2) Metabolites produced within primary and secondary lung tumor microenvironments dictate tumor immune escape and metastasis. To address our hypotheses, we propose the following two Specific Aims: Aim 1) To determine the efficacy of intranasal delivery of NP-based tumor vaccine as a prophylactic approach against metastatic lung lesions. Aim 2) To establish a metabolomics-based experimental approach used to define primary and metastatic tumor microenvironments. Through this collaborative Pilot Project with Dr. Byron Quinn of Langston University, we expect our findings we shed light of currently unknown mediators of anti- tumor responses that will be potentially useful in the development of novel immune-based targeted nanoparticle in cancer therapy. In addition, we anticipate that this pilot proposal will positively impact the building of a collaborative P20 in Cancer Research between Langston University and its partner, The University of North Texas Health Science Center.

摘要 大约90%的乳腺癌死亡是由转移到远处器官的肿瘤造成的。 在这些患者中，30-55%的患者发现了继发性肺转移，不幸的是，5年生存率 手术切除和放化疗的治愈率只有30-40%。这些糟糕的结果意味着一个关键的 需要进一步了解影响肿瘤转移的机制。我们研究的长期目标是 是设计创新的方法来提高免疫系统防止肺癌转移的能力 通过增加抗肿瘤免疫的知识。当前实施的基于免疫的策略 可溶性细胞因子和抗体已被引入临床和临床前试验，以广泛促进 对癌症的免疫反应。然而，非靶器官损伤和免疫耐受已显著 限制了它们的使用。基于粒子的纳米技术正在成为操纵免疫的一种可行方法 功能。然而，我们并不完全了解这些成分是如何影响免疫表型和 作为肿瘤细胞逃逸的预测因子和使用纳米颗粒的有效性可能有助于提高免疫力 心理治疗。基于先前的文献发现和本申请中描述的我们自己的初步发现， 我们的中心假设是：1)CPG鼻腔给药结合在NP包膜的表面 肿瘤抗原诱导保护性肺粘膜免疫保护抗肺肿瘤继发转移 2)原发和继发肺肿瘤微环境中产生的代谢产物指示肿瘤 免疫逃逸和转移。为了解决我们的假设，我们提出了以下两个具体目标： 目的1)确定鼻腔给药作为预防肿瘤疫苗的有效性。 抗转移性肺部病变。目的2)建立基于代谢组学的实验方法，用于 定义原发和转移的肿瘤微环境。通过与拜伦博士的合作试点项目 兰斯顿大学的奎因说，我们希望我们的发现揭示了目前未知的反-抗病毒介体 肿瘤反应将在基于免疫的新型靶向开发中潜在有用 纳米粒子在癌症治疗中的应用。此外，我们预计这项试点建议将对 兰斯顿大学及其合作伙伴在癌症研究方面的合作P20的建立 北得克萨斯大学健康科学中心。