ANTIPSEUDOMONAS VACCINE OF AUTOLOGOUS DENDRITIC CELLS CD40 LIGAND

本研究的主要目的是评估基因转移到造血干细胞（HSC）的慢性非球形细胞溶血性贫血（CNHSA）由于葡萄糖6-磷酸脱氢酶（G6 PD）缺乏症的患者的可行性和治疗效果。这种基因转移将提供足够的G6 PD产生的初步证据，导致改善外周血细胞计数和减少慢性溶血CNSHA患者。第二个目的是评估G6 PD缺乏引起的CNSHA患者自体移植后未进行骨髓消融的移植物植入程度和转导HSC的持久性。此外，为了提供表型校正的细胞将具有优于G6 PD缺陷型宿主骨髓的选择性生长优势的证据。这是一项揭盲的初步研究，使用重组逆转录病毒载体进行离体转导，将人G6 PD（GDPD cDNA）的编码序列导入患者的HSC。自体转导的骨髓将在不进行骨髓消融的情况下得到强化。将入组6例因G6 PD缺乏而患有CNSHA的患者。虽然患有CNSHA的重度G6 PD缺乏症患者很少见，但他们与丙酮酸激酶缺乏症一起构成了大多数因酶病而患有CNSHA的患者。目前的方案为这种疾病的患者提供了一种可能的治愈方法，无需骨髓抑制调节或住院治疗。该研究还将为其他临床病症提供有价值的信息，因为用下文描述的逆转录病毒载体离体转导HSC的方案可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.