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.

这个小型企业技术转移（STTR）I期项目为黑色素瘤开发了一种新颖的具有成本效益的治疗方法，可在家中和偏远的地理位置进行治疗。该项目的重要性反映在每年被诊断出患有这种毁灭性皮肤癌的100,000名患者中，每年有8,000名患者因疾病而丧生。概念证明是迈向开发新疗法的一步，用于治疗III期和IV型黑色素瘤。总体目标是在组织和细胞水平上开发手术准确的药物递送，这将导致组织水平触发免疫反应，从而增强药物的影响。 与竞争治疗替代方案相比，该解决方案应大大减少副作用。该方法允许现成的交付，使居住在偏远地区的患者获得最先进的治疗。每年，在美国，每年花57亿美元用于黑色素瘤治疗。针对III期和IV疾病的药物占15亿美元（26％）。这个小型企业技术转移（STTR）项目旨在为可以治疗III和IV阶段黑色素瘤的超级载体证明概念证明。该应用采用月桂素 - 单苯甲酮来产生选择性的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的纳米级脂质体颗粒中，以进行选择性黑色素瘤。该设计通过将活性成分直接运输到肿瘤来最大程度地减少副作用，从而提高了功效。由于肿瘤细胞而不是健康组织选择性摄取纳米颗粒，并且仅在纳米颗粒进入溶酶体/黑色素体室时才释放超级载体含量，因此将主要感受到肿瘤的影响，即使不是仅限于肿瘤。酪氨酸酶将前药转化为喹酮，该喹酮可触发存在的黑色素体酶（S），以产生新抗原，具有T细胞可见性的增加。最终的直接和间接黑色素瘤细胞毒性构成了超级载体治疗成功的关键。低毒性，再加上简单的现成交付，增强了患者的生活质量。由于没有患者特定的剪裁就可以增强免疫活动，因此该应用可以方便起见和有吸引力的成本比率。预计柔性，接近家庭的药物输送，几乎没有副作用，低成本和预期寿命增强将建立该药物的声誉，推动需求。该奖项反映了NSF的法定任务，并认为值得通过基金会的知识分子的智力优点和更广泛的影响来通过评估来获得支持。