Core C: Correlative Sciences PDCS/TCSL

摘要核心C：相关科学 免疫基因疗法在预后极差的情况下显示出无与伦比的抗癌效果 病人。CLL患者自身T细胞在体内疗效的局限性，抗原逃逸相关的复发 ALL，一个汽车工程的T细胞库，在骨髓瘤中被肿瘤细胞超过，并且缺乏适当的肿瘤- AML中的选择性CAR引发了目前的提议，其中创新的方法有望 解决细胞免疫治疗中的上述挑战。我们的试验将是第一个使用 CRISPR/Cas9增强的免疫基因疗法在每个临床中治疗一些最具挑战性的病例 适应症；第一次使用CART细胞靶向两种不同的抗原；第一次针对正常供者的AML 靶向CD33的CART细胞，同时用CD33编辑的造血干细胞重新填充宿主。 研究体内动力学的中央相关科学实验室是细胞疗法成功的关键 输液产品的归巢(S)与肿瘤的反应和输注细胞的生物活性； Core C提供这种基于GCLP但又灵活的基础设施，以支持在此建议的临床试验，其中 SOP规定的分子、细胞和生化分析将由合格的人员进行审查， 并输入数据库进行汇总分析，以评估我们提议的试验的有效性并进行比较 之前在宾夕法尼亚大学进行的CART细胞试验。

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.