SBIR Phase I: Antibody Therapy that Targets Neoantigens in Acute Myeloid Leukemia via the Antibody Dependent Cell-mediated Cytotoxicity Mechanism of Natural Killer Cells

SBIR 第一期：通过抗体依赖性细胞介导的自然杀伤细胞的细胞毒性机制，针对急性髓性白血病新抗原的抗体疗法

• 批准号: 2246487
• 负责人: Marc Gillig
• 金额: $ 27.5万
• 依托单位: ENABLE LIFE SCIENCES LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2246487&HistoricalAwards=false
• 关键词: SBIR; Phase; Antibody; Therapy; Targets

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project focuses on the unique combination of cancer-specific antibodies and adoptive Natural Killer (NK) immune cells needed to offer personalizable cancer therapies. This innovation represents a platform technology that can spawn multiple innovative cancer treatments, which could positively impact life sciences innovation and, more importantly, advance the health and welfare of the global cancer population. This novel approach to immunotherapy of cancer is expected to be highly efficacious and, due to the specificity of its mechanism of action, virtually devoid of toxicity. This is significant in light of the fact that the national cost of cancer care is in the $200 billion range.This project seeks to provide a unique combination of cancer-specific antibodies and adoptive Natural Killer (NK) immune cells that synergize to achieve high efficacy, avoid toxicity to healthy cells, and offer a scalable, resource-efficient and personalizable therapy for cancer. The project focus is antibody targeting of a neoantigen found exclusively in diseased Acute Myeloid Leukemia (AML) cancer cells, in order to develop an effective treatment for relapsed / refractory disease. The 30-50 candidate antibodies will be generated and tested by first immunizing rats, isolating the resulting antigen-specific B cells using a specialized fluorescence-activated cell sorting technique, sequencing and cloning the antibody genes, and expressing the antibodies in producer cells. Candidate antibodies will be tested for specificity (enzyme-linked immunosorbent assay) and binding strength (surface plasmon resonance) for the neoantigen target, whittling down the list to ~15 candidate antibodies. Further screening will be achieved by evaluating antibody induction of AML cell-specific killing by NK cells; readouts will include AML target cell death measured by flow cytometry and lactate dehydrogenase release, degranulation by NK cells (indicating killing activity), and cytokine release. The top-performing 3-5 candidates will eventually be selected for preclinical testing.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.

这项小型企业创新研究（SBIR）I期项目的更广泛的影响/商业潜力重点介绍了癌症特异性抗体和收养天然杀手（NK）免疫细胞所需的独特组合，需要提供可实现的癌症疗法。 这项创新代表了一种平台技术，该技术可以产生多种创新的癌症治疗方法，这可能会对生命科学创新产生积极影响，更重要的是，提高了全球癌症人群的健康和福利。这种新型癌症免疫疗法的方法有望高效，并且由于其作用机理的特异性实际上没有毒性。鉴于癌症护理的全国成本在2000亿美元范围内，这一点很重要。该项目旨在提供癌症特异性抗体和收养自然杀手（NK）免疫细胞的独特组合，以达到高效性，避免对健康细胞的毒性，并提供可伸缩，资源有效的，可伸缩的，可伸缩的，可扩展的，可扩展的癌症治疗。该项目的重点是针对新抗原的抗体，仅在患病的急性髓样白血病（AML）癌细胞中发现，以开发有效的复发 /难治性疾病治疗方法。将通过先免疫大鼠来生成和测试30-50种候选抗体，使用专门的荧光激活的细胞分选技术，测序和克隆抗体基因，并在生产者细胞中表达抗体。候选抗体将测试针对新抗原靶标的特异性（酶联免疫吸附测定）和结合强度（表面等离子体共振），并将其降低至约15种候选抗体。通过评估NK细胞对AML细胞特异性杀伤的抗体诱导，将实现进一步的筛查；读数将包括通过流式细胞术和乳酸脱氢酶释放，NK细胞脱粒（表明杀伤活性）和细胞因子释放测量的AML靶细胞死亡。最终将选出表现最佳的3-5名候选人进行临床前测试。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。