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

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是开发一类新的肿瘤治疗药物，称为“抗肿瘤免疫重定向剂（AIR）”。AIR将通过先前的儿童疫苗接种或过去的感染获得的身体预先存在的免疫应答重定向到靶向肿瘤细胞以根除癌症。在全球范围内，癌症仍然是五大主要死亡原因之一，导致对新疗法和治疗的高度未满足需求。免疫检查点抑制剂药物的阻断已成为一种有效的解决方案，并已证明具有临床益处。然而，这种治疗是昂贵和有毒的。此外，许多患者由于缺乏抗肿瘤反应而不合格、不响应或获得对此类药物的抗性。相比之下，我们的策略使患者的肿瘤对预先存在的抗病原体或儿童疫苗免疫敏感。我们的方法将改变或延长许多癌症患者的治疗机会。这也规避了在识别和/或产生针对癌症的有效免疫应答方面的风险和昂贵的研发挑战。 这个小企业创新研究（SBIR）第二阶段项目推进了一种领先的AIR的开发，这种AIR可以在体外和体内用小鼠肿瘤模型将不同的病毒免疫记忆反应重定向到肿瘤。第二阶段将推进开发：（1）将对我们目前的产品和纯化方法进行先进的优化和表征研究，以进一步确定与规模化生产兼容的一致工艺;（2）我们将启动更深入的非临床安全性和毒理学研究，以确保AIR解决方案达到所需的安全属性;以及（3）我们将在动物肿瘤模型中进行更多的体内研究，这些研究与最初的目标应用更加一致。建议的方法可能作为一个“现成的”免疫疗法的基础上，病人的个人健康/疫苗的历史，从而扩大额外的治疗机会，以更广泛的癌症患者population.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop a new class of oncology therapeutics termed “Anti-tumor Immune Redirectors (AIR)”. AIRs redirect the body’s pre-existing immune response obtained through previous childhood vaccination or past infections to target tumor cells for cancer eradication. Globally, cancer continues to be one of the top five leading causes of death, resulting in a high unmet need for novel therapies and treatments. Blockade of immune checkpoint inhibitor drugs have emerged as a potent solution with demonstrated clinical benefits. However, such treatments are expensive and toxic. Furthermore, many patients are ineligible, do not respond, or acquired resistance to such drugs due to the absence of an anti-tumor response. In contrast, our strategy tailors the patient’s tumor to become susceptible toward pre-existing anti-pathogenic or childhood vaccine immunity. Our approach will change or extend treatment opportunities for many cancer patients. This also circumvents the risky and costly R&D challenges in identifying and/or producing potent immune responses against cancer. This Small Business Innovation Research (SBIR) Phase II project advances the development of a lead AIR that could redirect different viral immune memory responses toward tumors in vitro, and in vivo with mouse tumor models. Phase II will advance the development: (1) Advanced optimization coupled with characterization studies will be performed on our current product and purification methods to further define a consistent process compatible with scaled manufacturing; (2) we will initiate more in-depth non-clinical safety and toxicology studies to ensure the AIR solution achieves the required safety attributes; and (3) we will perform additional in vivo studies in animal tumor models more aligned with the initial target application. The proposed approach potentially serves as an “off the shelf” immunotherapy based on the patient’s individual health/vaccine history, thereby extending additional treatment opportunities to a broader cancer patient population.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.