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; 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细胞工程为特异性T细胞受体（TCRS）的T细胞（TCRS），包括树突状细胞（DC）疗法，包括树突状细胞（DC）疗法（TCR）。 该实验室正在努力改善用于生产骨髓基质细胞（BMSC）的方法，并诱导多能茎（IPS）细胞用于再生医学应用。 树突状细胞是癌症疫苗的重要佐剂。 CCE目前正在生产表达HER2/NEU的DC来治疗肿瘤表达这种抗原的癌症患者。该实验室发现，血浆中某些人的因素可以抑制DC的HER2/NEU表达。 CCE新生产管理（NPM）实验室已经开发并正在制造多种CAR T细胞疗法。为了治疗B细胞白血病的小儿患者，正在制造CD22-CAR T细胞和CD19/CD19/CD22-双特异性T细胞。 最近启动了CD30卡车T细胞的制造。这些CAR T细胞用于治疗成人用淋巴瘤治疗。 该实验室还开发了抗B细胞成熟抗原（BCMA）CAR T细胞和抗SlamF7-CAR T细胞，以治疗患有多发性骨髓瘤的患者。 该实验室已经开发了使用完全自动化的仪器制造CD19/CD22- CAR T细胞的程序。 该自动化仪器已用于开发抗glypican-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实验室已经开发了一种产生表达T细胞受体（TCR）的T细胞的方法，该细胞对HPV-16癌蛋白E7具有特异性。这些细胞将用于治疗与HPV相关的宫颈和口咽癌的患者。该实验室最近还完成了KK-LC-1特异性TCR工程T细胞的开发。这些细胞还将用于治疗与HPV相关癌症患者。 细胞加工实验室正在与国家眼科研究所的研究人员合作，以开发从与血液分离的CD34+细胞生产IPS细胞并在视网膜色素上皮（RPE）细胞中区分IPS细胞的方法。 RPE细胞将用于治疗与年龄相关的黄斑变性的患者。