SBIR Phase I: Engineered B-cell Therapeutics for the Early Detection and Treatment of High-risk Breast Cancer

SBIR 第一期：用于早期检测和治疗高危乳腺癌的工程 B 细胞疗法

• 批准号: 2206743
• 负责人: Steven Deitcher
• 金额: $ 25.6万
• 依托单位: BESPOKE BIOTHERAPEUTICS LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2206743&HistoricalAwards=false
• 关键词: SBIR; Phase; Engineered; cell; Therapeutics

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project involves creation of a new, immune-cell-based treatment to address the unmet physical and psychological health needs of women with locally advanced (Stage III) breast cancer at high risk for relapse following standard-of-care surgery and drug therapy. Called cancer sentinels, these “living drugs” are made from patient blood-derived B-cells that have been isolated, chemically activated, and genetically modified to selectively seek and destroy residual breast cancer cells before they form detectable tumors and spread to vital organs. Cure is dependent on early detection and cancer cell elimination prior to distant spread. These engineered therapeutics may promote the destruction of breast cancer cells in multiple ways, including activation of immune system and the secretion of cancer-killing antibodies. Additional solid tumor cancer types, such as colorectal cancer, lung cancer, and ovarian cancer may also be addressable by future cancer sentinel products. In total, greater than 200,000 American cancer patients each year may benefit. This Small Business Innovation Research (SBIR) Phase I project addresses unmet needs of nearly 50,000 American women annually who are subjected to anxiety, fear, and lifestyle disruption because of newly diagnosed, locally advanced breast cancer. Emotional toxicity, beginning at cancer diagnosis, tends to peak during standard “watch and wait” cancer surveillance and the relapse uncertainty that follows initial surgical resection and post-surgery adjuvant therapy. This project combines the natural and unique antigen binding, lymph node-homing, antigen presentation, protein secretion, T-cell co-stimulation, and immune memory capabilities of human B-cells with large-cargo, non-viral, CRISPR/Cas9 and homology-mediated end joining-based genome editing techniques, to create cancer sentinels. Cancer sentinels are intended to destroy residual and relapsed breast cancer cells by locally secreting engineered anti-cancer antibodies and/or cytokines at the time of minimal residual cancer and prior to distant metastasis. To achieve such a multi-functional B-cell drug, autologous blood-derived B-cells will be genetically modified to express surface B-cell receptors (BCRs) with affinity for specific tumor-associated antigens (TAAs). Engineered BCR binding to TAAs may trigger local secretion of the engineered anti-cancer response molecules. Detection of these response molecules in the blood may also serve as a biomarker and alert physicians to the presence of residual cancer.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.

这个小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力涉及创建一种新的基于免疫细胞的治疗方法，以解决患有局部晚期（III期）乳腺癌的女性未满足的身体和心理健康需求。标准护理手术和药物治疗后复发风险高。这些被称为癌症哨兵的“活药物”是由患者血液来源的B细胞制成的，这些B细胞已被分离，化学活化和遗传修饰，以选择性地寻找和破坏残留的乳腺癌细胞，然后形成可检测的肿瘤并扩散到重要器官。治愈取决于早期发现和在远处扩散之前消除癌细胞。这些工程治疗可以通过多种方式促进乳腺癌细胞的破坏，包括激活免疫系统和分泌癌症杀伤抗体。其他实体瘤癌症类型，如结直肠癌、肺癌和卵巢癌也可能通过未来的癌症前哨产品来解决。总的来说，每年有超过20万美国癌症患者可能受益。这项小型企业创新研究（SBIR）第一阶段项目每年解决近50，000名美国妇女的未满足需求，这些妇女因新诊断的局部晚期乳腺癌而遭受焦虑，恐惧和生活方式破坏。从癌症诊断开始的情绪毒性，往往在标准的“观察和等待”癌症监测期间达到顶峰，以及在初次手术切除和术后辅助治疗之后的复发不确定性。该项目将人类B细胞的天然和独特的抗原结合，淋巴结归巢，抗原呈递，蛋白质分泌，T细胞共刺激和免疫记忆能力与大负荷，非病毒，CRISPR/Cas9和同源介导的末端连接基因组编辑技术相结合，以创建癌症哨兵。癌症哨兵旨在通过在最小残留癌症时和远处转移之前局部分泌工程化抗癌抗体和/或细胞因子来破坏残留和复发的乳腺癌细胞。为了获得这样的多功能B细胞药物，自体血液来源的B细胞将被遗传修饰以表达对特异性肿瘤相关抗原（TAA）具有亲和力的表面B细胞受体（BCR）。工程化的BCR与TAA的结合可以触发工程化的抗癌应答分子的局部分泌。检测血液中的这些反应分子也可以作为一种生物标志物，并提醒医生存在的残留cancer.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。