Development of a salt-based nanomedicine for non-muscle invasive bladder cancer

开发用于非肌肉浸润性膀胱癌的盐基纳米药物

• 批准号: 10482565
• 负责人: Zhi Liu
• 金额: $ 39.99万
• 依托单位: ATHNA BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-05 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10482565
• 关键词: Ablation; Affect; Aftercare; Apoptosis; BCG Live; Biochemical; Biotechnology; Bladder; Bladder Neoplasm; Breast; Bypass; Cancer Model; Cancerous; Catheters; Cell membrane; Cells; Clinical; Cytosol; Data; Development; Dose; Drug Kinetics; Endocytosis; Epithelial Cells; Equilibrium; Failure; Formulation; Head and neck structure; Histologic; Hour; Immune checkpoint inhibitor; Immune response; In Vitro; Ions; Label; Lipids; Liver; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Mitomycin C; Modeling; Morbidity - disease rate; Mus; Muscle; Osmotic Shocks; Outcome; Patients; Pharmaceutical Preparations; Phase; Phospholipids; Procedures; Prognosis; Prostate; Quality of life; Radical Cystectomy; Recurrence; Recurrent tumor; Refractory; Residual Cancers; Risk; Route; Rupture; Scheme; Sodium Chloride; Technology; Testing; Therapeutic; Therapeutic Index; Toxic effect; Transurethral Resection; Treatment Cost; Tumor Immunity; Urethra; Urine; Water; anti-cancer; base; cancer cell; cancer diagnosis; cancer therapy; cancer type; chemotherapy; cytotoxicity; efficacy evaluation; efficacy testing; first-in-human; high risk; immunogenic cell death; in situ vaccine; intravesical; mouse model; nanocrystal; nanomedicine; nanoparticle; nanoparticle delivery; non-muscle invasive bladder cancer; particle; preclinical study; prevent; side effect; standard care; systemic toxicity; tumor; tumor growth

Abstract Bladder cancer comprises 7% of new cancer diagnoses in the US. It is the sixth most prevalent malignancy, and has the highest lifetime treatment costs among all cancer types due to the need for lifelong surveillance. Early stage bladder cancer, also known as non-muscle-invasive bladder cancer (NMIBC), represents 75% of new bladder cancer cases. The standard treatment is transurethral resection of bladder tumor (TURBT), followed by intravescical therapy with chemotherapeutics such as mitomycin C or Bacille Calmette-Guérin (BCG). However, ~30% patients are refractory to BCG. Chemotherapies are assocaited with relatively high recurrence rates and ineffective as a second-line treatment for patients unresponsive to BCG. Meanwhile, no new intravesical drugs have been approved since 1998. There is an unmet clinical need for new NMIBC therapies. Athna Biotech, Inc. is developing a sodium chloride nanoparticle (SCNP) based cancer therapeutic. SCNPs deliver large amounts of Na+ and Cl- into cancer cells, by doing so disrupts the osmotic balance across the plasma membrane. Uniquely, SCNPs induce immunogenic cell death or ICD. This means that SCNPs essentially produce a vaccine in situ out of dying cancer cells, eliciting an antitumor immunity that prevents tumor recurrence and progression. SCNPs are intravesically instilled into the affected bladder to kill residual cancer cells after TURBT. After the treatment, SCNPs degrade to constitute ions that are excreted in the urine. The procedure is safe and can be applied repeatedly without causing local or systemic toxicity. In Phase I, we will test the efficacy of SCNPs in a mouse orthotopic bladder cancer model. In Phase II, we will evaluate the efficacy of SCNPs in an expanded pre-clinical study and perform IND-enabling pharmacokinetics and toxicity studies.

摘要 膀胱癌占美国新诊断癌症的7%。它是第六大最常见的恶性肿瘤， 由于需要终身监测，因此在所有癌症类型中，终身治疗成本最高。 早期膀胱癌，也被称为非肌肉浸润性膀胱癌，占75% 新增膀胱癌病例。标准的治疗方法是经尿道膀胱肿瘤电切术(TURBT)，其次是 化疗药物如丝裂霉素C或卡介苗(BCG)。 然而，约30%的患者对卡介苗无效。化疗的复发率相对较高。 对于对卡介苗无反应的患者，作为二线治疗的比率和无效。与此同时，没有新的消息 自1998年以来，膀胱内药物一直被批准。对新的NMIBC疗法的临床需求尚未得到满足。 Athna Biotech，Inc.正在开发一种基于氯化钠纳米颗粒(SCNP)的癌症治疗药物。SCNPs 向癌细胞输送大量的Na+和Cl-，这样做会破坏整个细胞的渗透平衡 质膜。独一无二的是，SCNPs可诱导免疫原性细胞死亡或ICD。这意味着SCNPs基本上 从死亡的癌细胞中原位生产疫苗，引发抗肿瘤免疫，防止肿瘤复发 和进步。SCNPs被注入受影响的膀胱内，以杀死残留的癌细胞 TURBT。治疗后，SCNPs会降解成离子，然后从尿液中排出。程序是 安全，可重复使用，不会造成局部或全身毒性。在第一阶段，我们将测试疗效 在小鼠原位膀胱癌模型中发现SCNPs。在第二阶段，我们将评估SCNPs在 扩大临床前研究，并进行支持IND的药代动力学和毒性研究。