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

摘要 大约90%的乳腺癌死亡是由于转移性肿瘤扩散到远端器官。 继发性肺转移在30-55%的患者中被确定，不幸的是，5年生存率 手术切除和放化疗的成功率仅为30-40%。这些糟糕的结果表明， 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预防肺肿瘤转移的能力 通过增加抗肿瘤免疫的知识。目前基于免疫的战略， 可溶性细胞因子和抗体已被引入临床和临床前试验中，以广泛地增强 对癌症的免疫反应。然而，脱靶器官损伤和免疫耐受具有显著的 限制其使用。基于粒子的纳米技术正在成为一种可行的方法来操纵免疫 功能然而，我们并不完全了解这些成分如何影响免疫表型， 作为肿瘤细胞逃逸的预测因子，纳米颗粒使用的功效可以有益于改善免疫功能。 疗法根据以前的文献发现和我们自己在本申请中描述的初步发现， 我们的中心假设是：1）鼻内给药结合到NP包封的表面的CPG， 肿瘤抗原诱导保护性肺粘膜免疫对肺肿瘤转移的保护作用 和2）在原发性和继发性肺肿瘤微环境内产生的代谢产物决定肿瘤 免疫逃逸和转移。为了解决我们的假设，我们提出以下两个具体目标： 目的1）确定鼻内递送基于NP的肿瘤疫苗作为预防方法的效力 对抗转移性肺部病变目的2）建立一种基于代谢组学的实验方法， 定义原发性和转移性肿瘤微环境。通过与拜伦博士的合作试点项目， 奎因的兰斯顿大学，我们希望我们的研究结果，我们揭示了目前未知的中介抗- 肿瘤反应，这将是潜在的有用的开发新的免疫为基础的靶向 纳米粒子在癌症治疗中的应用此外，我们预计这项试点提案将对 在兰斯顿大学及其合作伙伴之间建立癌症研究合作P20， 北德克萨斯大学健康科学中心。

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.