IGF::OT::IGF FAILED TUBULIN INHIBITOR REFORMULATED AS LOCALIZED ADJUVANT THERAPY FOR HEAD AND NECK CANCER

QR206是QR206的继续开发，其中包括艾哌酮D (EpoD)，这是一种高毒性的游离化疗药物，重新配制成长效聚（乳酸-羟基乙酸）酸微粒，在肿瘤和淋巴结内提供6-8周的持续释放，用于治疗头颈部鳞状细胞癌（HNSCC）。肿瘤内（i.t）注射QR206以多分散的微颗粒形式递送EpoD，这些微颗粒既可以保留在肿瘤部位的大尺寸，也可以通过利用吞噬细胞（如apc）的迁移扩散到区域和淋巴组织。拟议的配方将减少治疗肿瘤所需的药物量和全身暴露量，从而减少副作用和全身毒性。拟议的ind启用研究将包括在携带已建立的口腔同源肿瘤的免疫活性BALB/c小鼠中进行剂量递增和生物分布研究（目标1和目标2分别）。成功的小鼠研究之后，将进行剂量递增的兽医试验，用单剂量QR206治疗猫的口腔鳞状细胞癌（目标3）。预期结果包括两种动物模型的有效性和安全性的建立，QR206的靶向机制和预期的生物分布得到确认。

Proposed is a continued development of QR206, which comprises epothilone D (EpoD), a highly toxic chemotherapy in its free form, reformulated into long acting poly(lactic-co-glycolic) acid microparticles that provide 6-8 weeks of sustained release within tumors and lymph nodes, as treatment of head and neck squamous cell carcinoma (HNSCC). Intratumoral (i.t.) injection of QR206 delivers EpoD in poly-disperse microparticles spanning both large sizes that remain trapped at the tumor site and small sizes that spread into regional and lymphoid tissues by harnessing the migration of phagocytic cells, such as APCs. The proposed formulation will reduce the amount of drug required to treat the tumor and the systemic exposure to it, thus reducing side effects and systemic toxicity. The proposed IND-enabling studies will include dose escalation and biodistribution studies in immunocompetent BALB/c mice bearing established oral syngeneic tumors (Objectives 1 and 2, respectively). Successful murine studies will be followed by a dose escalation veterinary trial conducted where oral squamous cell carcinomas in cats will be treated with single doses of QR206 (Objective 3). The expected results include establishment of the efficacy and safety in two animal models and confirming QR206's targeting mechanism and anticipated biodistribution.