Development of novel cell and gene therapies

新型细胞和基因疗法的开发

• 批准号: 9340948
• 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/9340948
• 关键词: Acute Graft Versus Host Disease; Adenoviruses; Adjuvant; Adult; Age related macular degeneration; Antibodies; Antigens; Autoimmune Diseases; Autologous; B-Cell Leukemia; B-Cell Lymphomas; B-Lymphocytes; BK Virus; Blood; Blood Platelets; Bone Marrow; CD19 gene; CD22 gene; CD34 gene; Cancer Patient; Cancer Vaccines; Cell Maturation; Cell Therapy; Cell physiology; Cells; Clinical; Clinical Treatment; Cytomegalovirus; Dendritic Cell Therapy; Dendritic Cells; Development; ERBB2 gene; Failure; Growth; Healed; Hematologic Neoplasms; Hematopoietic; Human Herpesvirus 4; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Infection prevention; Inflammatory Bowel Diseases; Institutes; Laboratories; Laboratory Research; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Marrow; Medicine; Methods; Multiple Myeloma; Myocardial Ischemia; Oncogenes; Patients; Peripheral Vascular Diseases; Plasma; Procedures; Process; Progressive Multifocal Leukoencephalopathy; Property; Protocols documentation; Reagent; Regenerative Medicine; Research Personnel; Stromal Cells; Structure of retinal pigment epithelium; T cell therapy; T-Cell Receptor; T-Lymphocyte; Tissues; Transfusion; Transplant Recipients; Tumor Antigens; Viral; Virus; Virus Diseases; Work; cellular engineering; chimeric antigen receptor; cytokine; fetal bovine serum; gene therapy; graft failure; healing; improved; induced pluripotent stem cell; instrument; malignant oropharynx neoplasm; novel; novel therapeutics; patient oriented; pediatric patients; sarcoma; scale up; stem; tissue regeneration; tumor

The Cell Processing laboratory 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 manufacture of Bone Marrow Stromal Cells (BMSCs) and induced pluripotent stem (iPS) cells for regenerative medicine applications. In addition, the laboratory is developing antigen-specific T cells to treat viral infections in immune suppressed patients. Dendritic cells are an important adjuvant for cancer vaccines. The Cell Processing Laboratory 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 cell processing laboratory has developed and is manufacturing several CAR T cell therapies. CAR T cells expressing CD19, CD19-CAR T cells, are being manufactured in order to treat pediatric patients with B cell leukemia. Manufacturing of CD19-CAR T cells using a humanized CD19 antibody has recently been initiated. These CAR T cells are being used to treat adults with B cell lymphomas. The laboratory has also developed and is manufacturing anti-GD2 CAR T cells to treat patients with sarcoma, anti-B Cell Maturation Antigen (BCMA) to treat patients with multiple myeloma and anti-CD22 CAR T cells to treat patient with CD19-negative B cell leukemia. Human Papillomavirus (HPV) infection is associated with a number of cancers. The 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. Bone marrow stromal cells (BMSCs) can inhibit in function and support tissue regeneration Preliminary studies suggest that acute graft versus host disease and autoimmune diseases can be treated with BMSCs. In addition, BMSCs secrete cytokines and growth factor that improve the healing of damaged tissue and BMSCs have used to treat patients with ischemic heart disease and peripheral vascular disease. The Cell Processing Laboratory has developed a bank of BMSCs products collected from healthy subjects that is being used to treat hematopoietic stem transplant patients with acute graft versus host disease or graft failure and inflammatory bowel disease. The lab has also developed a process to produce autologous BMSCs to treat patients with ischemic heart disease. The laboratory has investigated the use of platelet lysate in place of fetal bovine serum as a media supplement to support the growth and expansion of BMSCs. The laboratory has also investigated the effect of the degree of BMSC confluence at the end of the culture period on BMSC properties. The Cell Processing Laboratory is also collaborating with NEI investigators 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. The laboratory completed the development of a protocol to treat and prevent infections to CMV, EBV, adenovirus and BK virus using multiple virus specific T cells. A protocol to treat patients with progressive multifocal leukoencephalopathy(PML) using BK-specific viral T cells has been developed and patients are being treated.

细胞加工实验室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细胞疗法以及设计为特异性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（TCRS）。 该实验室正在努力改善骨髓基质细胞（BMSC）的生产，并诱导多能茎（IPS）细胞进行再生医学应用。 此外，实验室正在开发抗原特异性T细胞，以治疗免疫抑制的患者中的病毒感染。 树突状细胞是癌症疫苗的重要佐剂。细胞加工实验室目前正在生产表达HER2/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，血浆中某些人的因素可以抑制DC的HER2/NEU表达。 细胞加工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，正在制造表达CD19的CD19型T细胞的CAR T细胞。 最近启动了使用人源化CD19抗体制造CD19卡车T细胞。这些CAR T细胞用于治疗B细胞淋巴瘤的成年人。 该实验室还开发了抗GD2 CAR T细胞，以治疗患有肉瘤，抗B细胞成熟抗原（BCMA）的患者，以治疗患有多发性骨髓瘤和抗CD22 CAR T细胞的患者，以治疗患有CD19（CD19阴性B细胞）的患者。 人乳头瘤病毒（HPV）感染与许多癌症有关。该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。 骨髓基质细胞（BMSC）可以抑制功能并支持组织再生的初步研究表明，急性移植物与宿主疾病和自身免疫性疾病可以用BMSC治疗。此外，BMSC分泌细胞因子和生长因子，以改善受损组织和BMSC的愈合，用于治疗缺血性心脏病和周围血管疾病的患者。细胞加工实验室已经开发了一种从健康受试者中收集的BMSCS产品，该产品用于治疗患有急性移植物与宿主疾病或移植物衰竭和炎症性肠病的造血性茎移植患者。该实验室还开发了一种生产自体BMSC的过程，以治疗缺血性心脏病的患者。 该实验室研究了血小板裂解物代替胎牛血清作为支持BMSC的生长和扩展的培养基补充剂。该实验室还研究了培养期结束时BMSC汇合度对BMSC特性的影响。 细胞加工实验室还与NEI研究者合作开发了从血液中分离出的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。 实验室使用多种特异性T细胞完成了一项方案的制定，以治疗和防止感染CMV，EBV，腺病毒和BK病毒。已经开发了一种使用BK特异性病毒T细胞的进行性多灶性白细胞核病（PML）患者的方案，并正在治疗患者。