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

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力是开发一种新的癌症疗法，涉及将通过以前儿童接种疫苗获得的人体先前存在的免疫反应重新定向到靶向肿瘤细胞以根除癌症。在全球范围内，癌症仍然是前五大死亡原因，导致对新疗法和治疗的高度需求尚未得到满足。免疫检查点抑制剂药物已成为一种有效的解决方案，并显示出临床益处。然而，这种治疗方法昂贵且有毒，高达70%的癌症患者由于缺乏抗肿瘤反应而对此类药物没有反应。相比之下，拟议的策略使患者的肿瘤对自己先前存在的儿童疫苗免疫变得敏感。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。这也避免了在识别和/或产生针对癌症的有效免疫反应方面的高风险和昂贵的研发挑战。这个SBIR第一阶段项目建议开发一种平台技术来动员儿童疫苗产生的免疫，并将这一活动重新引导到肿瘤上，以根除癌症。这将通过两个发展目标来实现。第一个目标将展示拟议技术动员现有儿童疫苗反应的能力，小鼠(具有相关的人类遗传)接种儿童疫苗(MMR、乙肝、水痘疫苗)。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能被根除。具体地说，小鼠将接种适当的儿童疫苗，然后注射相关的同基因肿瘤。一旦肿瘤被确定，建议的治疗方法将被注射，看看它是否可以诱导从儿童疫苗发展而来的先前存在的免疫，并重新定向到肿瘤。治疗效果将根据转移的数量和肿瘤重量/体积进行评估。如果成功，该平台将为多种癌症提供肿瘤特异性和广泛的适用性。

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.