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

CM-CX1治疗卵巢透明细胞癌和肾细胞癌的临床前开发

基本信息

批准号：
10682800
负责人：
Joana M Murad
金额：
$ 71.27万
依托单位：
CELDARA MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-08 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10682800
关键词：
ARHGEF5 gene Angiogenesis Inhibitors Antibodies Antigens Biological Assay Biological Markers CAR T cell therapy CD19 gene Cause of Death Cell Surface Proteins Cell Therapy Cell surface Cells Cessation of life Clear cell carcinoma Clear cell renal cell carcinoma Clinic Clinical Clinical Research Combination immunotherapy Coupled Cryopreservation Development Diagnosis Disease Dose Drug Side Effects Effectiveness Evaluation Exhibits Goals Hematologic Neoplasms High Prevalence Ideal 1 Immune checkpoint inhibitor Immune system Immunoglobulins Immunooncology Immunotherapy Infusion procedures Investigation Killer Cells Lead Legal patent Lymphocyte Malignant Neoplasms Malignant neoplasm of ovary Maximum Tolerated Dose Modality Mucin 1 protein Newly Diagnosed Normal tissue morphology Organ Ovarian Ovarian Carcinoma Ovarian Clear Cell Tumor Patients Peripheral Blood Mononuclear Cell Phase Process Production Refractory Renal Cell Carcinoma Renal carcinoma Retroviridae Risk Safety Schedule Signal Transduction Site Solid Neoplasm Specificity T-Lymphocyte Technology Transfer Therapeutic Time Tissues Toxic effect Tumor Antigens Tyrosine Kinase Inhibitor United States Urogenital Cancer Validation Virus Work antibody inhibitor cancer cell cancer heterogeneity candidate marker cell bank cellular targeting checkpoint therapy chemokine chemotherapy chimeric antigen receptor chimeric antigen receptor T cells cytokine cytotoxic density design effective therapy experience first-in-human genetically modified cells glycoprotein CX 1 immunogenic improved improved outcome in vivo manufacturing facility mortality mouse model neoplastic neoplastic cell novel novel strategies novel therapeutics optimism personalized cancer therapy phase 1 study pre-clinical preclinical development rat KIM-1 protein receptor binding side effect success survival outcome tumor urogenital tract weapons

项目摘要

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.

项目摘要癌症是全球死亡的主要原因之一。多年来，许多常规的细胞毒性已经开发出肿瘤性疾病的方法。但是，由于它们的有效性有限根据癌细胞的异质性，不断寻找治疗方法改善的预后，例如利用和增强患者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或“热” 癌症，因为肿瘤被T细胞浸润。这提供了对免疫系统可以是利用是对这些癌症的潜在耐用武器。嵌合抗原受体（CAR）T细胞疗法代表了个性化癌症的主要进步治疗。在此策略中，患者自己的T细胞经过基因设计以表达合成接收器结合肿瘤抗原。我们已经开发了一种汽车T细胞疗法CM-CX1，旨在针对一个非常肾脏和卵巢癌中的特定标记（TIM-1）。在健康组织中TIM-1的表达仅限于缺席的。这个快速提议的目的是确定CM-CX1归档所需的临床前工作用于首次人类评估的IND。