Preclinical development of CM-CX1 for the treatment of ovarian clear cell and renal cell carcinomas

项目总结 癌症是世界范围内主要的死亡原因之一。多年来，一些常规的细胞毒 治疗肿瘤疾病的方法已经开发出来。然而，由于它们在以下方面的效力有限 根据癌细胞的异质性，人们不断地寻找治疗方法 改善结果，例如利用和增强患者的正常能力的免疫疗法 免疫系统。值得注意的是，肾细胞癌和卵巢癌被认为是免疫原性的，或“热”的。 癌症，因为肿瘤中有T细胞的渗透。这让人们乐观地认为，免疫系统可以 被利用成为对抗这些癌症的有力和持久的武器。 嵌合抗原受体(CAR)T细胞疗法是个体化癌症的重大进展 治疗。在这一策略中，患者自己的T细胞被基因工程改造为表达一种合成受体 它能结合肿瘤抗原。我们已经开发出一种CAR T细胞疗法，CM-CX1，旨在针对非常 肾癌和卵巢癌特异性标志物(TIM-1)的检测TIM-1在健康组织中的表达仅限于 缺席。此快速通道提案的目标是最终完成CM-CX1提交的临床前工作 第一次人类评估的IND。

PROJECT SUMMARY Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. Of note, renal cell carcinoma and ovarian cancer are considered immunogenic, or “hot” cancers, in that tumors are infiltrated with T cells. This provides optimism that the immune system can be harnessed to be a potent and durable weapon against these cancers. Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement in personalized cancer treatment. In this strategy, a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. We have developed a CAR T cell therapy, CM-CX1, designed to target a very specific marker (TIM-1) in renal and ovarian cancers. Expression of TIM-1 in healthy tissues is limited to absent. The goal of this Fast Track proposal is to finalize the preclinical work required for CM-CX1 filing of an IND for first-in-human evaluation.