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.

幼年型粒单核细胞白血病 (JMML) 是一种罕见的儿童早期血液恶性肿瘤，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。影响幼儿，最常见于 4 岁以下儿童。目前，对大多数 JMML 患者唯一有效的治疗方法是同种异体造血然而，对于 JMML 儿童来说，HSCT 后复发的风险很大，因为一旦出现肿瘤逃逸变异，40-50% 的患者会出现疾病复发。 Gencyte Therapeutics, Inc. 提议开发一种逻辑门控精密分子适配器 (PMA) 系统，用于 JMML 治疗。通过概念授予阶段的工作，该平台技术可能会降低 CAR-T 毒性并防止复发。将建立用于 JMML 治疗的逻辑门控 PMA CAR 平台，并获得关键的初步概念验证数据，这将使这种潜在广泛适用的免疫治疗技术走向下一阶段的进一步开发。一般来说，CAR 靶向疗法如果成功，将产生一个具有广泛适用性的有前途的治疗平台，为临床前和临床开发做好准备。 目标 1：开发针对我们专有的结合表位和 PMA 的 scFv 抗体，用于肿瘤靶向 目标2.逻辑门控CAR慢病毒的生成 目标3：制备逻辑门控CAR-T细胞和靶细胞 目标 4：通过体外测定评估对数门控 PMA CAR 系统的 JMML 肿瘤细胞杀伤效率。