Core C: Correlative Sciences PDCS/TCSL

核心 C：相关科学 PDCS/TCSL

• 批准号: 9982259
• 负责人: Jan J Melenhorst
• 金额: $ 1.54万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9982259
• 关键词: Address; Adverse event; Aliquot; Antigen Targeting; Antigens; Biochemical; Biological; Biological Assay; Biological Markers; Biology; Blood; CAR T cell therapy; CD19 gene; CD22 gene; CRISPR/Cas technology; Calibration; Cause of Death; Cell Therapy; Cells; Cellular immunotherapy; Cerebrospinal Fluid; Childhood Acute Lymphocytic Leukemia; Clinical; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Correlative Study; Data; Databases; Detection; Development; Disease; Drug Kinetics; Enzyme-Linked Immunosorbent Assay; Equipment; Failure; Flow Cytometry; Future; Gene Expression; Genes; Goals; Heavy-Chain Immunoglobulins; Hematologic Neoplasms; Hematopoietic; Hematopoietic stem cells; Homing; Human Resources; Immune; Immunologic Monitoring; Immunophenotyping; Infrastructure; Infusion procedures; Kinetics; Laboratories; Laboratory Study; Lymphoid; Malignant Neoplasms; Marrow; Methods; Molecular; Monitor; Multiple Myeloma; Myelogenous; Natural Killer Cells; Patients; Population; Practice Guidelines; Procedures; Process; Relapse; Research; Running; Sampling; Science; Serum; Sorting - Cell Movement; Specific qualifier value; T-Lymphocyte; Technology; Tissues; Toxic effect; Training; anti-cancer; assay development; base; biobank; central database; chimeric antigen receptor T cells; cytokine; cytokine release syndrome; data management; deep sequencing; engineered T cells; gene therapy; immune reconstitution; immuno-gene therapy; in vivo; innovation; neoplastic cell; operation; outcome forecast; predictive modeling; receptor; reconstitution; research and development; response; success; tool; translational study; trial comparing; tumor

SUMMARY CORE C: CORRELATIVE SCIENCES Immuno-gene therapies have demonstrated an unparalleled anti-cancer efficacy in very poor prognosis patients. Limitations in the in vivo efficacy of the patient’s own T cells in CLL, antigen escape-related relapse in ALL, a CAR-engineered T cell pool outpaced by tumor cells in myeloma, and lack of appropriate, tumor- selective CAR in AML has given rise to the current proposal wherein innovative approaches are expected to solve the aforementioned challenges in cellular immunotherapy. Our trials will be the first to use CRISPR/Cas9-enhanced immune-gene therapy to treat some of the most challenging cases in each clinical indication; the first to use CART cells targeting two different antigens; the first to target AML with normal donor CART cells targeting CD33 while repopulating the host with CD33-edited hematopoietic stem cells. Critical to the success of cell therapies is a central correlative sciences laboratory to study the in vivo kinetics and homing of the infusion product(s) and the response of the tumor and the bioactivity of the infused cells; Core C provides this GCLP-based yet nimble infrastructure to support the clinical trials proposed herein, where SOP-specified molecular, cellular, and biochemical assays will be performed, reviewed by qualified personnel, and entered into a database for aggregate analysis to evaluate the efficacy of our proposed trials and compare with previously run CART cell trials at UPenn.

核心内容C：相关科学 免疫基因疗法在极差的预后中显示出无与伦比的抗癌疗效 患者患者自身T细胞在CLL中的体内功效的局限性， ALL是一种CAR工程化T细胞池，在骨髓瘤中被肿瘤细胞超越，并且缺乏适当的肿瘤- 反洗钱中的选择性CAR引发了目前的建议，其中创新方法预计将 解决了细胞免疫疗法中的上述挑战。我们的试验将是第一个使用 CRISPR/Cas9增强的免疫基因疗法，以治疗每个临床领域中一些最具挑战性的病例 适应症;第一个使用靶向两种不同抗原的CART细胞;第一个用正常供体靶向AML 靶向CD 33的CART细胞，同时用CD 33编辑的造血干细胞重建宿主。 细胞疗法成功的关键是一个研究体内动力学的中心相关科学实验室 以及输注产品的归巢和肿瘤的反应以及输注细胞的生物活性; Core C提供了这种基于GCLP但灵活的基础设施，以支持本文提出的临床试验，其中 将进行SOP规定的分子、细胞和生化测定，并由合格人员进行审查， 并输入数据库进行汇总分析，以评估我们提出的试验的有效性， 之前在宾夕法尼亚大学进行的CART细胞试验。