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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的膀胱癌占美国新诊断癌症的 7%，它是第六大常见恶性肿瘤。由于需要终身监测，因此在所有癌症类型中具有最高的终生治疗费用。早期膀胱癌，也称为非肌层浸润性膀胱癌 (NMIBC)，占 75% 新发膀胱癌病例的标准治疗是经尿道膀胱肿瘤切除术 (TURBT)，然后进行。通过膀胱内化疗药物如丝裂霉素 C 或卡介苗 (BCG) 进行治疗。然而，约 30% 的患者对 BCG 化疗无效，且复发率相对较高。对于对 BCG 无反应的患者来说，作为二线治疗无效，同时，没有新的治疗方案。膀胱灌注药物自 1998 年以来已获得批准。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 SCNP 的癌症治疗剂。将大量的 Na+ 和 Cl- 输送到癌细胞中，从而破坏细胞内的渗透压平衡独特的是，SCNP 会诱导免疫原性细胞死亡或 ICD。用垂死的癌细胞原位生产疫苗，引发抗肿瘤免疫力，防止肿瘤复发 SCNPs被注入膀胱内以杀死残留的癌细胞。 TURBT 治疗后，SCNP 降解形成离子，并通过尿液排出。安全，可以重复使用，不会引起局部或全身毒性。在第一阶段，我们将测试疗效。在第二阶段，我们将评估 SCNP 在小鼠原位膀胱癌模型中的功效。扩大临床前研究并进行支持 IND 的药代动力学和毒性研究。