Cell Prep Core

细胞制备核心

基本信息

批准号：
8554078
负责人：
John Wunderlich
金额：
$ 143.6万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
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/8554078
关键词：
Address Adoptive Immunotherapy Annual Reports Antigens Biological Response Modifiers Cancer Histology Cancer Patient Cell Therapy Cell physiology Cells Characteristics Clinical Clinical Protocols Clinical Trials Disseminated Malignant Neoplasm Enrollment Environment Genes Genetic Goals Human Human Papillomavirus Immune Immunotherapy In Vitro Laboratories Laboratory Research Life Lymphocyte Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Metastatic Melanoma Methodology Modeling Modification National Cancer Institute Operative Surgical Procedures Outcome Parents Patients Population Process Production Research Research Activity Research Personnel Research Project Grants Resources Sampling Serum Services Speed T-Lymphocyte Testing Therapeutic Time Translating Treatment Efficacy anticancer activity cancer cell cancer regression cancer therapy cost effective improved melanoma patient population pre-clinical programs standardize measure tumor

项目摘要

The purpose of this core resource facility is to provide ongoing support for the clinical immunotherapy program in the Surgery Branch of the National Cancer Institute. The laboratory is managed by two co-investigators, Drs. Mark Dudley and John Wunderlich, and each investigator has submitted the same annual report. The major effort in the laboratory is producing, ex vivo, large numbers of human anticancer T lymphocytes that are used in adoptive cell therapy for patients enrolled in Surgery Branch clinical trials. All of the patients have metastatic cancer, primarily melanoma. Commonly, ten to fifty billion cells are used for each treatment. The anticancer cells are generated in vitro from each patient's lymphocytes. The lymphocytes have natural anticancer activity, or anticancer activity induced or enhanced by genetic modification of the cells in vitro. Seventy six patients with metastatic cancer have been treated with anticancer lymphocytes during FY12 through August 1. During part or all of this same period of time, twenty one different clinical trials devoted to these therapies have been active and supported by the core laboratory.The core laboratory has also carried out research activities to improve its services. Thus, efforts have continued 1) to simplify the cell production methodology and make the process easier and more cost effective, 2) to relate characteristics of the anticancer lymphocytes and their parent populations to clinical outcomes following their use for treating patients, and 3) to help translate preclinical adoptive immunotherapy models, developed in the Surgery Branch and elsewhere, into new clinical protocols. Finally, the core laboratory continues to process cells and sera collected from cancer patients for a variety of uses, in addition to generating the anticancer cells described above. The products are routinely analyzed by investigators in the Surgery Branch immunotherapy program to evaluate progress toward the goals of each immunotherapy clinical trial, as well as to address subsequent research questions that help identify changes needed in the clinical trials. The samples are also used by Surgery Branch investigators for specific laboratory research projects that may translate into new patient therapies. These research projects include 1) transducing patients T cells with new genes whose products will provide better tumor recognition or otherwise enhance the cells anticancer functions, 2) evaluating the ability of infused anticancer lymphocytes to survive and function in the patient, 3) identifying new cancer antigens that are recognized by patients anticancer cells, 4) identifying characteristics of infused anticancer T cells that relate to cancer regression as measured by standardized, objective criteria, 5) identifying common characteristics of patients with metastatic cancer who are more likely to respond to adoptive cell therapy, 6) evaluating selected biological response modifiers tested in Surgery Branch clinical trials, and 7) extending adoptive cell therapy to additional types of metastatic cancer (e.g., cancers of the gastrointestinal tract and cancers induced by human papillomavirus).

该核心资源设施的目的是在国家癌症研究所的手术分支机构中为临床免疫疗法计划提供持续的支持。该实验室由两个共同研究员Drs管理。马克·达德利（Mark Dudley）和约翰·旺德利希（John Wunderlich），每个调查员都提交了相同的年度报告。实验室的主要努力是生产，离体，大量的人类抗癌T淋巴细胞，这些淋巴细胞用于手术分支分支机构临床试验的患者。所有患者患有转移性癌症，主要是黑色素瘤。通常，每种治疗都使用10至50亿个细胞。抗癌细胞是由每个患者的淋巴细胞在体外产生的。淋巴细胞具有天然抗癌活性，或者通过体外的遗传修饰引起或增强抗癌活性。在12财年至8月1日期间，已经用抗癌淋巴细胞治疗了76例转移性癌症患者。在一部分或整个期间，二十一项专门用于这些疗法的临床试验的二十架不同的临床试验已受到核心实验室的活跃和支持。因此，努力一直持续1）简化细胞生产方法并使过程更容易，更具成本效益，2）将抗癌淋巴细胞及其家长的特征与治疗患者治疗后的临床结果相关联，以及3），以帮助将陶立式的收养免疫治疗模型转化为在手术分支和其他临床方案中开发的。最后，除了产生上述抗癌细胞外，核心实验室继续处理从癌症患者那里收集的细胞和血清。研究人员在手术分支机构免疫疗法计划中常规分析产品，以评估朝着每项免疫疗法临床试验目标的进展，并解决随后的研究问题，以帮助确定临床试验中所需的变化。手术分支研究人员还将样品用于特定的实验室研究项目，这些项目可能转化为新的患者疗法。这些研究项目包括1）用新基因转导患者T细胞，其产物将提供更好的肿瘤识别或以其他方式增强细胞抗癌功能，2）评估注入抗癌淋巴细胞在患者中生存和功能的能力，3）鉴定由患者识别的抗药性细胞识别抗抗癌细胞的新癌症，4）鉴定出抗抗癌细胞，4）抗抗癌细胞，4）标准，5）确定更有可能对收养细胞治疗反应的转移性癌患者的共同特征，6）评估在手术分支机构临床试验中测试的选定的生物反应修饰剂，以及7）将收养细胞疗法扩展到其他类型的转移性癌症（例如，胃肠道和癌症的癌症）诱导的人类Papillomavirir诱导的癌症（例如，癌症）。