SBIR Phase I: Anti-Tumor Immune Redirectors (AIRs) for cancer treatment

SBIR 第一阶段：用于癌症治疗的抗肿瘤免疫重定向器 (AIR)

• 批准号: 1746588
• 负责人: Joshua Wang
• 金额: $ 22.5万
• 依托单位: PathoVax
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1746588&HistoricalAwards=false
• 关键词: SBIR; Phase; Anti; Tumor; Immune

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a new class of cancer therapeutics that involves the re-directing of the body's pre-existing immune response obtained through previous childhood vaccination to target tumor cells for cancer eradication. Globally, cancer continues to be a top 5 leading cause of death resulting in a high unmet need for novel therapies and treatments. Immune checkpoint inhibitor drugs have emerged as a potent solution with demonstrated clinical benefits. However, such treatments are expensive and toxic, and up to 70% of cancer patients do not respond to such drugs due to the absence of an anti-tumor response. In contrast, the proposed strategy tailors the patient's tumor to become susceptible towards their own pre-existing childhood vaccine immunity. This approach will change treatment outcomes for many cancer patients previously un-targetable by current immuno-therapeutic drugs. This also circumvents the risky and costly R&D challenges in identifying and/or producing potent immune responses against cancer.This SBIR Phase I project proposes to develop a platform technology to mobilize immunity generated from childhood vaccines and re-direct this activity towards tumors to eradicate cancer. This will be done via two development aims. The first aim will demonstrate the ability of the proposed technology to mobilize existing childhood vaccine responses from mice (with relevant human genetics) vaccinated with childhood vaccines (MMR, HepB, Chickpox vaccines). The second aim will be to test whether cancers with known metastasis challenges, such as ovarian and breast cancer, may be eradicated. Specifically, mice will be vaccinated with an appropriate childhood vaccine, then injected with relevant syngeneic tumors. Once the tumor is established, the proposed therapeutic will be injected to see if it can induce pre-existing immunity developed from the childhood vaccine and redirected towards the tumor. Therapeutic effect will be assessed based on the number of metastases and tumor weight/volume. If successful, this platform will provide both tumor specificity and broad applicability to a wide variety of cancers.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发一类新的癌症治疗方法，涉及重新定向通过以前的儿童疫苗接种获得的身体预先存在的免疫反应，以靶向肿瘤细胞，从而根除癌症。在全球范围内，癌症仍然是五大主要死亡原因之一，导致对新型疗法和治疗的高度未满足需求。免疫检查点抑制剂药物已成为一种有效的解决方案，并已证明具有临床益处。然而，这种治疗是昂贵的和有毒的，高达70%的癌症患者不响应这些药物由于缺乏抗肿瘤反应。相比之下，所提出的策略使患者的肿瘤变得对他们自己预先存在的儿童疫苗免疫敏感。这种方法将改变许多癌症患者的治疗结果，这些患者以前无法通过目前的免疫治疗药物进行靶向治疗。该SBIR第一阶段项目提出开发一种平台技术，以调动儿童疫苗产生的免疫力，并将这种免疫力重新导向肿瘤，以根除癌症。这将通过两个发展目标来实现。 第一个目标将证明拟议技术动员接种儿童疫苗（MMR、HepB、水痘疫苗）的小鼠（具有相关人类遗传学）的现有儿童疫苗应答的能力。第二个目标将是测试具有已知转移挑战的癌症，如卵巢癌和乳腺癌，是否可以根除。具体而言，小鼠将接种适当的儿童疫苗，然后注射相关的同源肿瘤。一旦肿瘤建立，将注射拟议的治疗药物，看看它是否可以诱导从儿童疫苗中产生的预先存在的免疫力，并重新导向肿瘤。将根据转移瘤数量和肿瘤重量/体积评估治疗效果。如果成功，该平台将为各种癌症提供肿瘤特异性和广泛的适用性。