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%。它是第六大流行恶性肿瘤， 并且由于需要终身监测，在所有癌症类型中具有最高的终身治疗成本。 早期膀胱癌，也称为非肌层浸润性膀胱癌（NMIBC），占75%， 新的膀胱癌病例。标准治疗是经尿道膀胱肿瘤切除术（TURBT）， 通过膀胱内化疗，如丝裂霉素C或卡介苗（BCG）。 然而，约30%的患者对BCG无效。化疗与相对较高的复发率相关 率和无效作为二线治疗的患者对卡介苗无反应。同时，没有新的 自1998年以来，膀胱内药物已被批准。对于新的NMIBC疗法存在未满足的临床需求。 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 将大量的Na+和Cl-输送到癌细胞中，这样做会破坏整个细胞的渗透平衡。 质膜独特地，SCNP诱导免疫原性细胞死亡或ICD。这意味着SCNP本质上 从垂死的癌细胞中原位产生疫苗，引发抗肿瘤免疫，防止肿瘤复发 和进步。将SCNP膀胱内滴注到受影响的膀胱中，以杀死术后残留的癌细胞。 TURBT。在治疗后，SCNP降解为构成在尿液中排泄的离子。该过程 安全，可重复使用，不会引起局部或全身毒性。在第一阶段，我们将测试 SCNP在小鼠原位膀胱癌模型中的作用。在第二阶段，我们将评估SCNP在一个 扩展临床前研究，并进行IND使能药代动力学和毒性研究。