STTR Phase I: Monobenzone (MBEH) Supercarriers: Production and Melanoma Treatment

STTR 第一阶段：莫诺苯宗 (MBEH) 超级载体：生产和黑色素瘤治疗

• 批准号: 2327009
• 负责人: Kettil Cedercreutz
• 金额: $ 27.5万
• 依托单位: TEMPRIAN ONCOLOGY, INC.
• 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: 2023-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2327009&HistoricalAwards=false
• 关键词: STTR; Phase; Monobenzone; MBEH; Supercarriers

This Small Business Technology Transfer (STTR) Phase I project develops a novel cost-effective treatment for melanoma that allows treatment delivery both at home and in remote geographic locations. The importance of the project is reflected in the 100,000 individuals that are diagnosed with this devastating skin cancer annually as well as by 8,000 patients a year being lost to the disease. The proof of concept is a step towards the development of a novel therapy for the treatment of stage III and IV melanoma. The overarching goal is to develop surgically accurate drug delivery at both the tissue and cellular levels that will result in a tissue-level triggering of an immune response that heightens the impact of the drug. The solution should drastically decreased side effects when compared to competing treatment alternatives. The method allows for off-the-shelf delivery, giving patients living in remote locations access to state-of-the-art therapy. Annually, $5.7 billion is spent on melanoma treatment in the US. Drugs targeting stage III and IV disease make up $1.5 billion (26%). This Small Business Technology Transfer (STTR) project aims to demonstrate proof of concept for supercarriers that will treat stage III and IV melanomas. The application employs lauroyl-monobenzone to produce selective anti-melanoma action and effective immune activation, packaging the drug in biocompatible nanoscale liposomal particles for selective melanoma delivery. The design enhances efficacy while minimizing side effects by transporting the active ingredient directly to the tumor. Due to the selective uptake of nanoparticles by tumor cells rather than healthy tissues, and because supercarrier contents are released only when the nanoparticles enter the lysosomal/melanosomal compartment, the impact will be felt primarily, if not exclusively, by the tumor. Tyrosinase converts the prodrug into a quinone that haptenizes the melanosomal enzyme(s) present to generate neoantigens with increased visibility for T cells. The resulting direct and indirect melanoma cytotoxicity form the key to supercarrier treatment success. Low toxicity, combined with simple off-the-shelf delivery, enhance patient quality of life. As enhanced immune activity comes without patient-specific tailoring, the application allows for convenience and an attractive cost-to-quality ratio. Flexible, close-to-home drug delivery, few side effects, low cost, and enhanced life expectancy are expected to build the reputation of the drug, propelling the demand.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.

这项小型企业技术转移（STTR）第一阶段项目开发了一种新的具有成本效益的黑色素瘤治疗方法，可以在家中和偏远地区进行治疗。每年有10万人被诊断患有这种毁灭性的皮肤癌，每年有8 000名患者死于这种疾病，这反映了该项目的重要性。这个概念的证明是朝着开发一种治疗III期和IV期黑色素瘤的新疗法迈出的一步。总体目标是在组织和细胞水平上开发手术精确的药物递送，这将导致组织水平触发免疫反应，从而增强药物的影响。与其他治疗方案相比，这种解决方案应该会大大减少副作用。这种方法允许现成的交付，使生活在偏远地区的患者能够获得最先进的治疗。在美国，每年用于黑色素瘤治疗的费用高达57亿美元。针对III期和IV期疾病的药物占15亿美元（26%）。这项小型企业技术转移（STTR）项目旨在证明超级载体治疗III期和IV期黑色素瘤的概念。该应用程序采用月桂醇-单苯酮产生选择性抗黑色素瘤作用和有效的免疫激活，将药物包装在生物相容性纳米级脂质体颗粒中，用于选择性黑色素瘤递送。这种设计通过将活性成分直接输送到肿瘤中，提高了疗效，同时最大限度地减少了副作用。由于纳米颗粒是由肿瘤细胞而不是健康组织选择性摄取的，而且只有当纳米颗粒进入溶酶体/黑素体隔室时，超载体内容物才会被释放，因此这种影响主要（如果不是完全）是由肿瘤感受到的。酪氨酸酶将前药转化为醌，醌使黑素体酶发生半抗原，从而产生对T细胞具有更高可见性的新抗原。由此产生的直接和间接的黑色素瘤细胞毒性是超级载体治疗成功的关键。低毒性，加上简单的现成交付，提高了患者的生活质量。由于增强的免疫活性无需针对患者进行定制，因此该应用程序提供了便利性和具有吸引力的成本-质量比。灵活、就近给药、副作用少、成本低、预期寿命延长等因素有望建立药物的声誉，从而推动需求。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。