Development of novel cell and gene therapies

细胞处理实验室正在努力开发和改进癌症细胞疗法，包括树突状细胞(DC)疗法、嵌合抗原受体(CAR)T细胞疗法和经工程改造的表达肿瘤抗原特异性T细胞受体(TCR)的T细胞。该实验室正在努力改进骨髓基质细胞(BMSCs)和诱导多能干细胞(IPS)的制造，以用于再生医学应用。此外，该实验室正在开发抗原特异性T细胞来治疗免疫抑制患者的病毒感染。 树突状细胞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，用于治疗肿瘤表达该抗原的癌症患者。该实验室发现，一些人血浆中的因子可以抑制DC表达HER2/neu。 细胞处理实验室已经开发并正在制造几种汽车T细胞疗法。表达CD19的CAR T细胞，CD19-CAR T细胞，正在被制造出来用于治疗患有B细胞白血病的儿童患者。使用人源化的CD19抗体制造CD19-CAR T细胞最近已经开始。这些CAR T细胞正被用于治疗成人B细胞淋巴瘤。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。 人乳头瘤病毒(HPV)感染与许多癌症有关。该实验室已经开发出一种方法来生产T细胞，该T细胞表达针对HPV-16癌蛋白E7的T细胞受体(TCR)。这些细胞将用于治疗HPV相关的宫颈癌和口咽癌患者。 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。该实验室研究了用血小板裂解液替代胎牛血清作为支持骨髓间充质干细胞生长和扩增的培养液补充。实验室还研究了培养结束时骨髓间充质干细胞融合程度对骨髓间充质干细胞性能的影响。 细胞处理实验室还与NEI研究人员合作，开发从血液中分离的CD34+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(RPE)细胞。RPE细胞将用于治疗老年性黄斑变性患者。 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)患者的方案已经开发出来，患者正在接受治疗。

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.