Tumor Targeted Nanobins for the Treatment of Metastatic Breast and Ovarian Cancer

描述(申请人提供)：转移性三阴性乳腺癌和卵巢癌是目前缺乏有效治疗的致命疾病。最近开发的纳米颗粒形式的活性药物，包裹在脂质和聚合试剂中，导致了一种被称为纳米双宾的平台。先导剂显著提高了有效化疗药物的有效性和安全性。事实证明，这些纳米生物素能够安全地将有效的一线抗癌药物，如三氧化二砷，安全地输送到肿瘤中，比母体药物具有更好的疗效，导致治疗指数显著提高。这个纳米技术平台的既定效力来自被动的、基于EPR的和基于表位的分子靶向策略。一个由化学家、肿瘤生物学家、材料科学家、妇科肿瘤学家和翻译科学家组成的跨学科团队将把这些先导剂推向临床。同时，他们将开发新的纳米酶制剂，将其他有效的抗癌药物，如顺铂，与针对肿瘤特异性表位的表面拴系抗体结合在一起。建议的药物还将能够将多种致敏剂和细胞毒剂输送到实体肿瘤。这些药物将在一个实验矩阵中进行筛选，该矩阵包括几个乳腺癌和卵巢癌原位异种移植动物模型中的定量里程碑和纳米双宾的评估。这个跨学科团队将继续与NCI癌症纳米技术联盟的成员合作，评估来自其他机构的新平台，用于这些罕见的妇科和转移性乳腺癌的动物模型。这一平台伙伴关系的研究工作将由一名在将药物从发现阶段推进到IND申请和概念验证第二阶段试验方面具有专业知识的团队成员进一步加强和协调。这些研究的预期结果将是为治疗这些目前无法治愈的癌症开发安全有效的纳米材料。相关性(见说明)：癌症仍然是对数百万人福祉的重大健康挑战。需要开发治疗癌症的广泛创新的非传统治疗干预措施，以加快进展。这一应用将导致临床上有用的抗癌候选药物和基于纳米颗粒的药物的翻译管道。这些药物代表了一种新的药物输送模式，用于治疗罕见和难以治疗的癌症，如卵巢癌和转移性乳腺癌

DESCRIPTION (provided by applicant): Metastatic Triple negative breast cancer and ovarian cancer are lethal diseases that currently lack effective treatments. Recently developed nanoparticulate forms of active drugs, encapsulated in lipid and polymeric agents, have led to a platform known as nanobins. The lead agents provide dramatically increased efficacy and safety of validated chemotherapeutic agents. The proven ability of these nanobins to safely deliver potent, front line anticancer drugs, such as arsenic trioxide, to tumors with greater efficacy than the parent drugs results in a significantly higher therapeutic index. The established efficacy of this nanotechnology platform arises from both passive, EPR-based and epitope-based molecular targeting strategies. An interdisciplinary team of chemists, tumor biologists, materials scientists, gynecological oncologists, and translational scientists will advance the lead agents to the clinic. In parallel, they will develop new nanobin agents that combine other potent anticancer drugs, such as Cisplatin, with surface tethered antibodies that target tumor specific epitopes. The proposed agents will be also able to deliver multiple sensitizing and cytotoxic agents to solid tumors. The agents will be screened in an experimental matrix that includes quantitative milestones and evaluation of nanobins in several orthotopic xenograph animal models of breast and ovarian cancer. This interdisciplinary team will continue to collaborate with members of the NCI Alliance for Nanotechnology in Cancer to evaluate emerging platforms from other institutions in these animal models of rare gynecological and metastatic breast cancers. The research efforts of this Platform Partnership will be further augmented and coordinated by a team member with expertise in advancing drugs from the discovery stage to IND filings and to proof of concept phase 2 trials The anticipated outcome of these studies will be the development of safe and effective nanomaterials for the treatment of these currently incurable cancers. RELEVANCE (See instructions): Cancer continues to represent a significant health challenge to the well being of millions of people. Broadly innovative non-traditional therapeutic interventions for the treatment of cancer need to be developed in order to accelerate progress. This application will lead to clinically useful anti-cancer drug candidates and a translational pipeline of nanoparticle based drugs. These agents represent a new paradigm in drug delivery for the treatment of rare and difficult to treat cancers such as ovarian and metastatic breast cancer