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癌症诊断的7％。这是第六大最患病率的恶性肿瘤，由于需要终生监测，因此在所有癌症类型中的终生治疗费用最高。早期膀胱癌，也称为非肌肉侵入性膀胱癌（NMIBC），占75％新的膀胱癌病例。标准治疗是膀胱肿瘤（TURBT）的尿道切除术通过化学治疗疗法（例如丝裂霉素C或Bacille Calmette-Guérin（BCG））的静脉治疗。但是，约有30％的患者对BCG难治性。化学疗法与相对较高的复发有关对于对BCG无反应的患者的二线治疗率和无效的率。同时，没有新的自1998年以来，已经批准了静脉注射药物。对新的NMIBC疗法的临床需求未满足。 Athna Biotech，Inc。正在开发基于氯化钠纳米颗粒（SCNP）的癌症治疗。 scnps 通过这样做，将大量的Na+和Cl-输送到癌细胞中，从而破坏跨整个质膜。 SCNP独特地诱导免疫原性细胞死亡或ICD。这意味着SCNPS本质上是从垂死的癌细胞中产生疫苗，引发抗肿瘤免疫（防止肿瘤复发）和进展。 SCNP插入室内灌输到受影响的膀胱中，以杀死残留的癌细胞涡轮治疗后，SCNP降解以构成尿液中额外的离子。过程是安全，可以反复应用而不会引起局部或全身毒性。在第一阶段，我们将测试效率小鼠原位膀胱癌模型中的SCNP。在第二阶段，我们将评估SCNP的效率扩展的临床前研究并进行了辅助药代动力学和毒性研究。