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

描述（由申请人提供）：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。最近开发的活性药物的纳米粒形式，封装在脂质和聚合剂中，导致了一个被称为纳米宾的平台。先导药物显著提高了化疗药物的有效性和安全性。经证实，这些纳米蛋白能够安全地将有效的一线抗癌药物（如三氧化二砷）输送到肿瘤中，其疗效比母体药物更高，从而显著提高治疗指数。这种纳米技术平台的有效性来自于被动的、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、妇科肿瘤学家和转化科学家组成的跨学科团队将把先导药物推向临床。与此同时，他们将开发新的纳米蛋白制剂，将其他强效抗癌药物（如顺铂）与靶向肿瘤特异性表位的表面绑定抗体结合起来。提出的药物也将能够提供多种致敏和细胞毒性药物实体瘤。这些药物将在实验基质中进行筛选，包括在几种原位乳腺癌和卵巢癌动物模型中对纳米蛋白的定量里程碑和评估。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，评估其他机构在这些罕见妇科和转移性乳腺癌动物模型中的新兴平台。这一平台合作伙伴关系的研究工作将进一步得到加强，并由一名在推进药物从发现阶段到IND申请和概念验证2期试验方面具有专业知识的团队成员进行协调。这些研究的预期结果将是开发出安全有效的纳米材料，用于治疗这些目前无法治愈的癌症。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。为了加快进展，需要开发用于治疗癌症的广泛创新的非传统治疗干预措施。这一应用将导致临床有用的抗癌候选药物和基于纳米颗粒的药物的转化管道。这些药物代表了治疗罕见和难以治疗的癌症（如卵巢癌和转移性乳腺癌）的药物递送新范式

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