Cell Prep Core

细胞制备核心

• 批准号: 9154293
• 负责人: John Wunderlich
• 金额: $ 88.66万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/9154293
• 关键词: Activated Lymphocyte; Address; Adoptive Cell Transfers; Annual Reports; Antigens; Area; B-Lymphocytes; Back; Biological Response Modifiers; Biopsy; Blood; Blood specimen; Cancer Histology; Cell Therapy; Cells; Characteristics; Clinical; Clinical Protocols; Clinical Trials; Cooperative Research and Development Agreement; Cost Savings; Cyclic GMP; Data; Disseminated Malignant Neoplasm; Effectiveness; Enrollment; Excision; Extramural Activities; Genes; Genetic Engineering; Goals; Growth; Head; Human; Human Resources; Immunotherapy; Institution; Laboratories; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of urinary bladder; Mission; Mutation; National Cancer Institute; Neoplasms; Operative Surgical Procedures; Outcome; Parents; Patients; Peripheral; Population; Process; Production; Protocols documentation; Research; Research Personnel; Research Project Grants; Resected; Sampling; Somatic Mutation; Source; T cell therapy; T-Lymphocyte; Testing; Therapeutic; Training; Translating; Translations; Tumor Antigens; Tumor-Infiltrating Lymphocytes; base; cancer therapy; commercialization; gene therapy; improved; in vivo; interest; malignant breast neoplasm; manufacturing process; melanoma; novel; pre-clinical; programs; success; synovial sarcoma; therapy development; tumor; tumor immunology

The mission of this core laboratory is to provide support to the immunotherapy program established by the Surgery Branch of the National Cancer Institute. The laboratory is managed by two co-investigators, Drs. Robert Somerville and John Wunderlich, and each investigator has submitted the same annual report. The main effort of the laboratory involves the production of large numbers of human anti-cancer T lymphocytes ex vivo, to treat patients with advanced metastatic cancer enrolled on Surgery Branch clinical trials. Cancer targeting lymphocytes are either isolated directly from biopsied material or are generated by genetically modifying T lymphocytes from a patient's blood. Eighty six patients on 17clinical trials have been treated with cell therapies generated by this core laboratory during FY15 through August 1st. Eighty three patients underwent resection to generate tumor infiltrating lymphocyte cultures for treatment and successful cultures were established for eighty of these patients. In addition to the labs manufacturing functions, research has 1) simplified and streamlined the manufacturing process resulting in cost savings 2) related characteristics of the anticancer lymphocytes and their parent populations to clinical outcomes 3) translated preclinical findings from other groups within the Surgery Branch in to novel clinical protocols 4) implemented a closed, fully cGMP compliant manufacturing process for one of clinical products for use by a CRADA partner in the commercialization of one this therapy 5) trained personnel from other institutions which are seeking to establish adoptive cell transfer therapy programs. A second critical function of this core lab is to collect, process, and curate samples from patients enrolled on Surgery Branch protocols. These samples are used to generate the cancer therapies described above and are also used by investigators in the Surgery Branch cell therapy program to evaluate the progress of each clinical trial, as well as to address research questions that identify changes that can be implemented to improve these trials. In addition, the samples from these trials facilitate research that generates new patient therapies. These research projects include 1) transducing patients' T cells with genes whose products will better target tumors or enhance endogenous tumor activity, 2) evaluating the ability of infused anticancer lymphocytes to function and survive in patients, 3) identifying new cancer associated antigens that can be targeted by anticancer cells, 4) Identifying novel patient specific antigens that are created by somatic mutations and selecting cultures that recognize these mutations for use in personalized T cell therapies 5) identifying characteristics of infused anticancer cells that are associated with objective tumor regression, 6) identifying characteristics of patients who are most likely to respond to anticancer T cell therapies, 7) Evaluating selected biological response modifiers tested in Surgery Branch clinical trials, 8) Extending anticancer cell therapies to other cancer histologies (lung, ovarian, breast and bladder cancers). Finally, the core laboratory maintains and curates all source documents, data, protocols and expertise associated with cGMP manufacturing and the clinical translation of anticancer cell therapies. Due to the success of these therapies developed by the Surgery Branch, investigators within the Surgery Branch, intramural NCI laboratories, extramural regulatory agencies, industrial and academic partners, and other interested parties increasingly want access to these data, protocols and advice. Robert Somerville is currently head of the Cell Production Facility at the National Cancer Institute in Bethesda, USA, where the main interest is to establish successful gene therapies and cell based treatments for patients with advanced metastatic cancer.

该核心实验室的任务是为国家癌症研究所手术部门建立的免疫疗法计划提供支持。该实验室由两个共同研究员Drs管理。罗伯特·萨默维尔（Robert Somerville）和约翰·旺德利希（John Wunderlich），每个调查员都提交了同样的年度报告。实验室的主要工作涉及生产大量人类抗癌淋巴细胞，以治疗参加手术分支机构临床试验的晚期转移性癌症患者。靶向淋巴细胞的癌症直接从活检材料中分离出来，或者是通过从患者血液中遗传改性的T淋巴细胞而产生的。在15财年至8月1日期间，该核心实验室产生的细胞疗法对17个临床试验的86例患者进行了治疗。为这些患者中的80例建立了83例切除术，以产生肿瘤浸润淋巴细胞培养物进行治疗和成功培养。 In addition to the labs manufacturing functions, research has 1) simplified and streamlined the manufacturing process resulting in cost savings 2) related characteristics of the anticancer lymphocytes and their parent populations to clinical outcomes 3) translated preclinical findings from other groups within the Surgery Branch in to novel clinical protocols 4) implemented a closed, fully cGMP compliant manufacturing process for one of clinical products for use by a CRADA partner in the commercialization of一种疗法5）来自其他机构的培训人员，他们正在寻求建立收养细胞转移疗法计划。该核心实验室的第二个关键功能是从参加手术分支方案的患者中收集，处理和策划样本。这些样品用于产生上述癌症疗法，并被研究人员在手术分支细胞疗法计划中使用，以评估每个临床试验的进度，并解决鉴定可以实施改善这些试验的变化的研究问题。此外，这些试验的样本有助于产生新的患者疗法的研究。这些研究项目包括1）用基因过滤患者的T细胞，其产物将更好地靶向肿瘤或增强内源性肿瘤活性，2）评估注入注入的抗癌淋巴细胞功能和生存的能力，在患者中发挥作用和生存 therapies 5) identifying characteristics of infused anticancer cells that are associated with objective tumor regression, 6) identifying characteristics of patients who are most likely to respond to anticancer T cell therapies, 7) Evaluating selected biological response modifiers tested in Surgery Branch clinical trials, 8) Extending anticancer cell therapies to other cancer histologies (lung, ovarian, breast and bladder cancers).最后，核心实验室维护并策划了与CGMP制造和抗癌细胞疗法的临床翻译相关的所有来源文档，数据，协议和专业知识。由于手术部门开发的这些疗法的成功，手术分支机构内的研究人员，壁内NCI实验室，壁外监管机构，工业和学术伙伴以及其他有关方面越来越希望越来越希望获得这些数据，协议和建议。罗伯特·萨默维尔（Robert Somerville）目前是美国贝塞斯达国家癌症研究所（National Cancer Institute）的细胞生产设施负责人，在那里，主要兴趣是为晚期转移性癌症患者建立成功的基因疗法和基于细胞的疗法。