Development of novel cell and gene therapies

新型细胞和基因疗法的开发

• 批准号: 9154063
• 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/9154063
• 关键词: Abnormal Cell; Acute Graft Versus Host Disease; Adenoviruses; Adjuvant; Affinity; Allogenic; Antigens; Autoimmune Diseases; Autologous; B-Lymphocytes; BK Virus; Bone Marrow; CD19 gene; CD22 gene; Cancer Patient; Cancer Vaccines; Cell Maturation; Cell Therapy; Cell physiology; Cells; Childhood; Chronic Lymphocytic Leukemia; Clinical; Cytomegalovirus; Dendritic Cells; Development; ERBB2 gene; Engineering; Failure; Growth Factor; Healed; Hematologic Neoplasms; Hematopoietic; Host Defense; Human Herpesvirus 4; Immune; Immune system; Infection prevention; Inflammatory Bowel Diseases; Laboratories; Laboratory Research; Legal patent; Malignant Neoplasms; Malignant neoplasm of prostate; Marrow; Medicine; Multiple Myeloma; Myocardial Ischemia; Natural Killer Cells; Papillomavirus; Patients; Peripheral Vascular Diseases; Play; Procedures; Process; Progressive Multifocal Leukoencephalopathy; Protocols documentation; Reagent; Research Personnel; Staging; Stromal Cells; T cell therapy; T-Cell Receptor; T-Lymphocyte; Tissues; Transfusion; Transplant Recipients; Viral; Virus; Work; base; chimeric antigen receptor; cytokine; gene therapy; graft failure; healing; improved; instrument; novel; patient oriented; sarcoma; scale up; stem; tissue regeneration; tumor

The cell processing laboratory is developing new natural killer (NK) cell, dendritic cell (DC), bone marrow stromal cell (BMSC) and chimeric antigen receptor (CAR) T cell therapies. NK cells are an important part of the innate immune system and they are thought play an important in host defense against foreign and abnormal cells including cancer and hematological malignancies. Preliminary work suggests that hematological malignancies can be treated by the administration of NK cells. The Cell Processing Laboratory has been expanding autologous and allogeneic NK cells to treat Clinical Center patients with cancer and hematological malignancies. Dendritic cells (DCs) are an important adjuvant for cancer vaccines. The Cell Processing Laboratory is currently is producing DCs expressing HER2/neu to treat cancer patients whose tumor express this antigen and is developing a new protocol to treat patients with stage 0 prostate cancer 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 cell processing laboratory has developed CAR T cells expressing anti-CD19. These cells are now being used to treat pediatric patents with B cell leukemias. 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. The lab is working on manufacturing engineered T cells which express a high affinity T cell receptor specific for papilloma virus. 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 is also being developed.

细胞处理实验室正在开发新的自然杀伤(NK)细胞、树突状细胞(DC)、骨髓基质细胞(BMSC)和嵌合抗原受体(CAR)T细胞疗法。 NK细胞是天然免疫系统的重要组成部分，被认为在抵抗外来细胞和异常细胞(包括癌症和血液系统恶性肿瘤)的宿主防御中发挥重要作用。初步研究表明，血液系统恶性肿瘤可以通过给药NK细胞来治疗。细胞处理实验室一直在扩大自体和同种异体NK细胞，以治疗临床中心癌症和血液系统恶性肿瘤患者。 树突状细胞(DC)是肿瘤疫苗的重要佐剂。细胞处理实验室目前正在生产表达HER2/neu的DC来治疗肿瘤表达这种抗原的癌症患者，并正在开发一种新的方案来治疗0期前列腺癌患者 骨髓基质细胞(BMSCs)具有抑制功能和支持组织再生的功能，初步研究表明，BMSCs可以治疗急性移植物抗宿主病和自身免疫性疾病。此外，BMSCs还能分泌细胞因子和生长因子，促进受损组织的愈合，BMSCs已被用于治疗缺血性心脏病和周围血管疾病。细胞处理实验室开发了一套从健康受试者身上收集的骨髓间充质干细胞产品，用于治疗患有急性移植物抗宿主病或移植物衰竭和炎症性肠病的造血干细胞移植患者。该实验室还开发了一种生产自体骨髓间充质干细胞的方法，用于治疗缺血性心脏病患者。 细胞处理实验室已经开发出表达抗CD19的CAR T细胞。这些细胞现在被用来治疗患有B细胞白血病的儿童患者。该实验室还开发并正在制造用于治疗肉瘤患者的抗GD2 CAR T细胞、用于治疗多发性骨髓瘤患者的抗B细胞成熟抗原(BCMA)和用于治疗CD19阴性B细胞白血病的抗CD22 CAR T细胞。该实验室正在致力于制造表达针对乳头状瘤病毒的高亲和力T细胞受体的工程T细胞。 该实验室完成了使用多个病毒特异性T细胞治疗和预防CMV、EBV、腺病毒和BK病毒感染的方案的开发。一种使用BK特异性病毒T细胞治疗进行性多灶性白质脑病(PML)患者的方案也在开发中。