SBIR Phase I: A single-cell-interaction platform for accelerating discovery of bispecific T-cell engagers

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力将成为发现治疗癌症的新免疫疗法的平台。对于人类的各种疾病，特别是癌症，最近批准的几种免疫疗法可以有效地治疗，在某些情况下，还可以治愈几种被认为是致命的癌症。不幸的是，目前可用的此类治疗方法屈指可数，而且成本很高。该项目旨在开发一种新技术，使生物制药和生物技术公司能够以更快、更具成本效益的方式发现下一代疗法，并有更高的成功机会。最终，该项目旨在帮助为免疫疗法带来更有效、更负担得起的选择，以造福于有未得到满足的医疗需求的患者。这项SBIR第一阶段是一项评估尖端单细胞相互作用平台技术的提案，旨在评估其加速发现免疫疗法的潜力，特别是双特异性T细胞结合蛋白(BITES)，这是一类经临床验证的双特异性抗体。BITS由两个不同的区域组成，可以同时与T细胞靶点和肿瘤靶点结合。BITES将T细胞与肿瘤细胞联系起来的独特能力使它们能够表现出更高的特异性和有效性，部分是通过一种新的作用模式，通过激活T细胞来杀死肿瘤细胞。然而，咬伤的开发过程非常缓慢，限制了它们在一系列破坏性疾病中的临床应用。该领域的一个反复出现的挑战是，缺乏一个强大的平台，能够以具有成本效益的方式快速有效地确定被铅咬伤的候选者。目前的提案旨在证明拟议的基于微流控的单细胞相互作用平台技术的技术和操作可行性，该技术可以以分区的分析形式直接询问许多单个咬合变体的功能。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be a platform to identify new immunotherpeutics for the treatment of cancer. For a variety of human diseases, cancer in particular, several recently approved immunotherapeutics can effectively treat and, in some cases, cure several forms of cancer that were considered fatal. Unfortunately, there are only a handful of these treatments currently available, and the cost is high. This project aims to develop a new technology that may empower biopharma and biotech companies to discover next generation therapeutics in an expeditious and cost-effective manner with a much higher chance of success. Ultimately, the project aims to help bring more efficacious and more affordable choices for immunotherapeutics to benefit patients with unmet medical needs. This SBIR Phase I is a proposal to evaluate a cutting-edge single-cell-interaction platform technology for its potential to accelerate the discovery of immunotherapeutics, specifically, the bispecific T cell engagers (BiTEs), a clinically validated class of bispecific antibodies. BiTEs consist of two distinct domains that can simultaneously bind to a T cell target and a tumor target. BiTEs' unique ability to link T cells to tumor cells allows them to exhibit improved specificity and efficacy, in part through a novel mode of action, by activating T cells to kill tumor cells. However, the development process for BiTEs has been very slow, limiting their clinical availability for a broad range of devastating diseases. A recurring challenge in the field is the lack of a robust platform that is capable of rapid and efficient identification of lead BiTE candidates in a cost-effective manner. The current proposal aims to prove the technical and operational feasibility of the proposed microfluidic-based single-cell-interaction platform technology that can directly interrogate the functions of many individual BiTE variants in a compartmentalized assay format.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.