NV103: Antibody Conjugated Nanoparticle for Ewing Sarcoma Targeted Therapy

这个第二阶段的SBIR项目试图证明新的、有针对性的纳米颗粒 能将治疗物质输送到人肿瘤细胞并减轻肿瘤负担 癌症。这些纳米颗粒的概念是基于杂化聚合的 展示靶向肿瘤细胞的功能性抗体的脂质体纳米粒(HPLN) 曲面标记。这些治疗性药物是封装的细胞毒性药物，包括 尤因肉瘤的一线治疗。一旦被肿瘤细胞识别， 纳米颗粒结合，被带进细胞(内吞)，纳米颗粒货物被 释放，最终允许获得杀死癌细胞的药物。这个项目很适合 在NCI的使命范围内，开发基于纳米技术的新疗法。 耐药转移是大多数癌症患者的最终死亡原因。 对于转移瘤的系统治疗通常是无效的。一种可靠、低毒、高度 迫切需要有效的治疗方法来治疗复发患者和耐药患者 转移瘤。因此，这项建议的具体目标是优化 HPLN颗粒，对体内靶向抗癌药物进行高效包埋 HPLN在人源化异种移植中显示出杀死癌细胞的安全性和有效性 人尤因肉瘤小鼠模型的建立。第一个目标是确定最大 健康动物的耐受量(MTD)及荷瘤动物的PK-效应关系 老鼠。NanoValent的目标是在第二阶段结束时拥有一个 可生产GMP的优化配方，随后收集 提交给FDA批准这一新疗法的IND所需数据。

This Phase II SBIR project seeks to demonstrate that novel, targetable nanoparticles can delivery therapeutic substances to human tumor cells and reduce tumor burden in cancer. The concept for these nanoparticles is based on the hybrid polymerized liposome nanoparticle (HPLN) that displays functional antibodies that target tumor cell surface markers. The therapeutic cargos are encapsulated cytotoxic drugs that comprise the front line treatment for Ewing sarcoma. Upon recognition by the tumor cell, the nanoparticle binds, gets taken into the cell (endocytosed) and the nanoparticle cargo is released, ultimately allowing availability of the drug to kill the cancer cell. This project fits well within the mission of the NCI, to develop new nanotechnology-based therapeutics. Treatment-resistant metastases are the ultimate cause of death in most cancer patients. Systemic therapy for metastases is generally ineffective. A reliable, low-toxic, highly effective therapy is urgently needed to treat both relapse patients and treatment-resistant metastases. The specific aims of this proposal are therefore to optimize the HPLN particle, carry out efficient encapsulation of cancer drugs inside the targeted HPLNs, demonstrate safety and efficacy in killing cancer cells in a humanized xenograft mouse model of human Ewing sarcoma. The first aim is to determine the maximal tolerated dose (MTD) in healthy animals and the PK-efficacy relationship in tumor-bearing mice. NanoValent’s goal, at the conclusion of the Phase II is to have an optimized formulation that can be GMP manufactured and subsequently gather the necessary data for an IND submission to the FDA for approval of this novel therapy.