ANTIPSEUDOMONAS VACCINE OF AUTOLOGOUS DENDRITIC CELLS EXPRESSING CD40 LIGAND

本研究的主要目的是评估基因转入造血干细胞（HSC）治疗葡萄糖6-磷酸脱氢酶（G6PD）缺乏症所致慢性非球型溶血性贫血（CNHSA）患者的可行性和治疗效果。该基因转移将提供初步证据，证明产生足够的G6PD可改善CNSHA患者的外周血计数并减少慢性溶血。第二个目的是评估G6PD缺乏症引起的CNSHA患者自体移植后移植物的植入程度和转导的HSC的持久性。此外，提供证据表明，表型校正细胞将有选择性生长优势比G6PD缺陷宿主骨髓。这是一项非盲性先导研究，利用重组逆转录病毒载体将人G6PD （GDPD cDNA）的相应序列转导到患者的HSC中。自体转导的骨髓将在不进行骨髓消融的情况下得到强化。6例因G6PD缺乏症导致的CNSHA患者将被纳入研究。虽然患有严重G6PD缺乏症的CNSHA患者很少，但它们与丙酮酸激酶缺乏症一起构成了大多数由酶病引起的CNSHA患者。目前的方案为这种疾病的患者提供了一种可能的治疗方法，无需骨髓抑制条件或住院治疗。这项研究也将为其他临床疾病提供有价值的信息，因为用下面描述的逆转录病毒载体体外转导HSC的方案可以应用于其他单基因疾病。

The primary purpose of this study is to assess the feasibility and therapeutic efficacy of gene transfer into the hematopoietic stem cells (HSC) of patients with chronic non-spherocytic hemolytic anemia (CNHSA) due to glucose 6-phosphate dehydrogenase (G6PD) deficiency. This gene transfer will provide preliminary evidence of the production of sufficient G6PD to cause improvement in peripheral blood counts and decrease in chronic hemolysis in CNSHA patients. The secondary aim is to evaluate the extent of engraftment and the persistence of the transduced HSC following autologous transplantation without myeloablation in CNSHA patients caused by G6PD deficiency. Furthermore, to provide evidence that the phenotypically corrected cells will have a selective growth advantage over the G6PD deficient host bone marrow. This is an unblinded pilot study using ex vivo transduction with a recombinant retroviral vector to transduce the cording sequence of the human G6PD (GDPD cDNA) into the patients' HSC. The autologous transduced bone marrow will be reinforced without myeloablation. Six patients with CNSHA due to G6PD deficiency will be enrolled. Although patients with severe with severe G6PD deficiency who have CNSHA are rare, they make up, together with pyruvate kinase deficiency, the majority of patients with CNSHA due to an enzymopathy. The current protocol provides a possible cure for patients in this disease without myelosuppressive conditioning or hospitalization. This study would also provide valuable information for other clinical conditions, as the protocol for ex vivo transduction of HSC with the retroviral vector delineated below could be applied to other monogenic disorders.