NV103: Antibody Conjugated Nanoparticle for Ewing Sarcoma Targeted Therapy

这个第二阶段SBIR项目旨在证明， 可以将治疗物质递送到人肿瘤细胞， 癌这些纳米颗粒的概念是基于混合聚合的 脂质体纳米颗粒（HPLN），其展示靶向肿瘤细胞的功能性抗体 表面标记。所述治疗性货物是包封的细胞毒性药物，其包含 尤文肉瘤的一线治疗一旦被肿瘤细胞识别， 纳米颗粒结合，进入细胞（内吞），纳米颗粒货物被 释放，最终允许药物的可用性杀死癌细胞。这个项目适合 这也是NCI的使命之一，就是开发新的纳米技术疗法。 耐药转移是大多数癌症患者死亡的最终原因。 全身治疗转移瘤通常无效。一种可靠、低毒、高 迫切需要有效的治疗来治疗复发患者和耐药患者。 转移因此，本提案的具体目标是优化 HPLN颗粒，将抗癌药物高效包裹在靶向药物内部， HPLN在人源化异种移植物中显示出杀死癌细胞的安全性和有效性 人尤文肉瘤的小鼠模型。第一个目标是确定最大的 健康动物的耐受剂量（MTD）和荷瘤动物的PK-疗效关系 小鼠NanoValent的目标，在第二阶段结束时， 优化的配方，可以GMP生产，并随后收集 向FDA提交IND申请以批准这种新疗法的必要数据。

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.