Cell Prep Core

细胞制备核心

基本信息

批准号：
8350108
负责人：
John Wunderlich
金额：
$ 119.76万
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/8350108
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 Immune Immunotherapy In Vitro Laboratories Laboratory Research Life Lymphocyte Malignant Neoplasms Melanoma Vaccine 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 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 patients lymphocytes. The lymphocytes have natural anticancer activity, or anticancer activity induced or enhanced by genetic modification of the cells in vitro. One hundred and ten patients with metastatic cancer were treated with anticancer lymphocytes during the last year. Sixteen different clinical trials are currently devoted to these treatments, as of September, 2011, and are 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 melanoma cancer antigens that are recognized by patients anticancer cells, 4) identifying characteristics of infused anti-cancer T cells that relate to melanoma cancer regression as measured by standardized, objective criteria, 5) identifying common characteristics of patients with melanoma who are more likely to respond to adoptive cell therapy, 6) evaluating melanoma vaccines developed in the Surgery Branch and tested in clinical trials, and 7) evaluating selected biological response modifiers tested in Surgery Branch clinical trials.

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。每个患者淋巴细胞在体外产生抗癌细胞。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。在过去的一年中，将一百十名转移性癌症患者用抗癌淋巴细胞治疗。截至2011年9月，目前有16例不同的临床试验专门研究这些治疗方法，并得到了核心实验室的支持。核心实验室还开展了研究活动以改善其服务。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）用新基因转导的患者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）评估患者中注入的抗癌淋巴细胞在患者中生存和功能的能力，3）鉴定出抗抗癌细胞的新型抗原，4）鉴定抗菌细胞识别抗药性抗原，4）抑制了抗药性的特征，4）抑制了抗药性的特征。通过标准化的客观标准衡量，5）确定黑色素瘤患者的共同特征，他们更有可能对收养细胞疗法反应，6）评估手术分支中开发的黑色素瘤疫苗并在临床试验中进行了测试，以及7）评估在手术分支机构临床试验中测试的选定的生物学反应修饰剂。