THE PURPOSE OF THIS MODIFICATION IS TO EXERCISE THE I-CORP OPTION

此修改的目的是行使 I-CORP 选择权

• 批准号: 10933819
• 负责人: CHUHUA ZHONG
• 金额: $ 35.5万
• 依托单位: GENCYTE THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-27 至 2024-02-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10933819
• 关键词: Affect; Age; Allogenic; Antibodies; Award; Binding; Cells; Child; Childhood Leukemia; Data; Development; Diagnosis; Epitopes; Exercise; Generations; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Immunotherapy; Juvenile Myelomonocytic Leukemia; Lentivirus; Logic; Modification; Molecular; Patients; Phase; Recurrent disease; Relapse; Risk; System; Technology; Therapeutic; Toxic effect; Tumor Escape; United States; Variant; Work; cell killing; chimeric antigen receptor T cells; clinical development; early childhood; effective therapy; experience; in vitro Assay; leukemia treatment; mortality; neoplastic cell; preclinical development; relapse prevention; targeted treatment; technology platform; tumor

Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy of early childhood with high mortality. JMML accounts for 1-2% of childhood leukemias each year; in the United States, an estimated 25-50 new cases are diagnosed each year. JMML predominately affects young children, most often developing in children under the age of 4. Currently, the only effective treatment for most JMML patients is allogeneic hematopoietic stem cell transplantation (HSCT). However, relapse is a significant risk after HSCT for children with JMML because once tumor escape variants are developed, there are no other treatments available. 40–50% of the patients experience disease recurrence. Gencyte Therapeutics, Inc. proposes developing a logic gate-controlled precision molecular adaptor (PMA) system, for JMML treatment. This proposed platform technology could potentially lower CAR-T toxicity during treatment and prevent relapse. Through the work of concept award phase, Gencyte will have established the logic gated PMA CAR platform for JMML treatment and obtained key preliminary proof-of-concept data that will move this potentially broadly applicable immunotherapy technology toward the further development next phase. These studies will advance CAR-targeted therapies in general and, if successful, yield a promising therapeutic platform with broad applicability that is ready for preclinical and clinical development. Objective 1: Develop scFv antibodies specific to our proprietary binding epitope and PMAs for tumor targeting Objective 2. Generation of lentivirus of logic-gated controlled CAR Objective 3: Preparing logic-gated controlled CAR-T cells and target cells Objective 4: Evaluating the JMML tumor cell killing efficiency of the log-gated PMA CAR system by in vitro assays.

少年脊髓细胞性白血病（JMML）是罕见的幼儿血液系统恶性肿瘤，死亡率很高。 JMML每年占儿童白血病的1-2％；在美国，估计每年诊断出25-50例新病例。 JMML主要影响幼儿，最常在4岁以下的儿童中发育。目前，大多数JMML患者的唯一有效治疗方法是同种异体造血干细胞移植（HSCT）。但是，由于肿瘤逃生变种，没有其他治疗可用，因此，HSCT后HSCT后的复发是一个重大风险。 40-50％的患者患有疾病复发。 Gencete Therapeutics，Inc。用于JMML治疗的逻辑栅极控制精密分子适配器（PMA）系统的建议。该提出的平台技术可能会在治疗过程中可能降低CAR-T毒性并防止退休。通过概念奖的工作阶段，Gencte将建立用于JMML治疗的逻辑门控PMA CAR平台，并获得了关键的初步概念证明数据，该数据将把这种潜在的广泛适用的免疫疗法技术转移到下一阶段的进一步发展。这些研究将一般可以推进靶向汽车的疗法，如果成功的话，将产生一个有望的治疗平台，其适用性广泛，可以用于临床前和临床发育。 目标1：开发针对我们专有结合表位和肿瘤靶向PMA的SCFV抗体 目标2。逻辑门控汽车的慢病毒产生 目标3：准备逻辑门控受控的CAR-T细胞和靶细胞 目标4：通过体外测定法评估日志门控PMA CAR系统的JMML肿瘤细胞杀死效率。