Development of novel cell and gene therapies

新型细胞和基因疗法的开发

• 批准号: 10471695
• 负责人: David Stroncek
• 金额: --
• 依托单位: CLINICAL CENTER
• 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/10471695
• 关键词: Adjuvant; Adult; Age related macular degeneration; Antigens; Autoimmune Diseases; B-Cell Leukemia; B-Lymphocytes; Blood; Bone Marrow; CAR T cell therapy; CD19 gene; CD22 gene; CD34 gene; Cancer Patient; Cancer Vaccines; Cell Maturation; Cell Separation; Cell Therapy; Cells; Clinical; Clinical Treatment; Deficiency Diseases; Dendritic Cell Therapy; Dendritic Cells; Development; ERBB2 gene; Failure; GPC3 gene; Hematologic Neoplasms; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Laboratories; Laboratory Research; Lymphoma; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Marrow; Methods; Multiple Myeloma; National Eye Institute; Oncoproteins; Patients; Plasma; Primary carcinoma of the liver cells; Procedures; Process; Production; Reagent; Regenerative Medicine; Research Personnel; Stromal Cells; Structure of retinal pigment epithelium; T-Cell Receptor; T-Lymphocyte; TNFRSF8 gene; Tumor Antigens; cellular engineering; chimeric antigen receptor T cells; engineered T cells; gene therapy; improved; induced pluripotent stem cell; instrument; malignant oropharynx neoplasm; novel; novel therapeutics; patient oriented; pediatric patients; scale up; tumor

The Center for Cellular Engineering (CCE) is working to develop and improve cancer cellular therapies including Dendritic Cell (DC) therapies, chimeric antigen receptor (CAR) T cell therapies and T cell engineered to express T cell receptors (TCRs) specific to tumor antigens. The laboratory is working to improve the methods used to produce Bone Marrow Stromal Cells (BMSCs) and induced pluripotent stem (iPS) cells for regenerative medicine applications. Dendritic cells are an important adjuvant for cancer vaccines. The CCE is currently producing DCs expressing HER2/neu to treat cancer patients whose tumors express this antigen. The lab has discovered that factors in the plasma from some people can inhibit the expression of HER2/neu by DCs. The CCE New Production Management (NPM) laboratory has developed and is manufacturing several CAR T cell therapies. CD22-CAR T cells and CD19/CD22-bispecific T cells are being manufactured in order to treat pediatric patients with B cell leukemia. Manufacturing of CD30-CAR T cells has recently been initiated. These CAR T cells are being used to treat adults with lymphomas. The laboratory has also developed anti-B Cell Maturation Antigen (BCMA) CAR T cells and anti-SLAMF7-CAR T cells to treat patients with multiple myeloma. The laboratory has developed procedures to manufacture CD19/CD22- CAR T cells using a completely automated instrument. This automated instrument has been used to develop anti-Glypican-3 CAR T cells which will be used to treat patients with hepatocellular carcinoma. Human Papillomavirus (HPV) infection is associated with a number of cancers. The NPM laboratory has developed a method to produce T cells that express a T cell receptor (TCR) that is specific for the HPV-16 oncoprotein E7. These cells will be used to treat patients with HPV-associated cervical and oropharyngeal cancers. The laboratory has also recently completed the development of KK-LC-1 specific TCR engineered T-cells. These cells will also be used to treat patients with HPV-associated cancers. The Cell Processing Laboratory is collaborating with investigators in the National Eye Institute to develop methods to manufacture iPS cells from CD34+ cells isolated from the blood and to differentiate the iPS cells in retinal pigment epithelial (RPE) cells. The RPE cells will be used to treat patients with age related macular degeneration.

细胞工程中心（CCE）正在努力开发和改善癌症细胞疗法，包括树突状细胞（DC）疗法，嵌合抗原受体（CAR）T细胞疗法和T细胞工程化表达T细胞受体（TCR）特异性肿瘤抗原。 该实验室正在努力改进用于生产骨髓基质细胞（BMSC）和诱导多能干细胞（iPS）的方法，用于再生医学应用。 树突状细胞是癌症疫苗的重要佐剂。CCE目前正在生产表达HER 2/neu的DC，以治疗肿瘤表达这种抗原的癌症患者。该实验室发现，某些人血浆中的因子可以抑制DC表达HER 2/neu。 CCE新生产管理（NPM）实验室已经开发并正在生产几种CAR T细胞疗法。正在生产CD 22-CAR T细胞和CD 19/CD 22-双特异性T细胞，以治疗患有B细胞白血病的儿科患者。 CD 30-CAR T细胞的制造最近已经开始。这些CAR T细胞被用于治疗患有淋巴瘤的成年人。 该实验室还开发了抗B细胞成熟抗原（BCMA）CAR T细胞和抗SLAMF 7-CAR T细胞，用于治疗多发性骨髓瘤患者。 该实验室已经开发了使用完全自动化的仪器制造CD 19/CD 22- CAR T细胞的程序。 这种自动化仪器已被用于开发抗磷脂酰肌醇蛋白聚糖-3 CAR T细胞，该细胞将用于治疗肝细胞癌患者。 人乳头瘤病毒（HPV）感染与许多癌症有关。NPM实验室已经开发出一种方法来产生表达T细胞受体（TCR）的T细胞，该受体对HPV-16癌蛋白E7具有特异性。这些细胞将用于治疗HPV相关的宫颈癌和口咽癌患者。该实验室最近还完成了KK-LC-1特异性TCR工程化T细胞的开发。这些细胞也将用于治疗HPV相关癌症患者。 细胞处理实验室正在与国家眼科研究所的研究人员合作，开发从血液中分离的CD 34+细胞制造iPS细胞的方法，并将iPS细胞分化为视网膜色素上皮细胞（RPE）。RPE细胞将用于治疗年龄相关性黄斑变性患者。