Publications by authors named "G M Podsakoff"
Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy [GT]). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a phase 2 clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND (myeloproliferative sarcoma virus, negative control region deleted, dl587rev primer binding site)-ADA gammaretroviral vector (gRV) and infused following busulfan reduced-intensity conditioning.
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- Acquired aplastic anemia (aAA) is a condition characterized by a deficiency in blood production and an increased risk of developing myelodysplastic syndrome and leukemia, likely driven by T cell immunity related to Human Leukocyte Antigen (HLA) class II pathways.
- Recent research using whole exome sequencing discovered significant mutations in HLA class I genes in some aAA patients, suggesting these mutations may play a crucial role in autoimmunity associated with the disease.
- The study found that 17% of screened aAA patients had somatic HLA class I losses and that specific HLA alleles (*14:02 and *40:02) were more common in aAA patients compared to controls; these mutations correlate with
Article Synopsis
- Autologous hematopoietic stem cell transplantation (HSCT) using gene-modified cells is an effective treatment for adenosine deaminase-deficient severe combined immunodeficiency (ADA-deficient SCID), particularly when combined with reduced intensity conditioning (RIC) and stopping enzyme replacement therapy (ERT).
- In a phase II study involving 10 patients, gene-modified stem cells were successfully transplanted, showing good clinical outcomes, including normalization of blood cell activity and improved immune responses.
- No serious complications occurred post-transplant, and many subjects remained free from further ERT, indicating strong safety and efficacy of the gene therapy approach.
Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells.
View Article and Find Full Text PDFAAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes.
Mol Ther Methods Clin Dev
October 2015
Adeno-associated virus (AAV) has become one of the most promising vectors in gene transfer in the last 10 years with successful translation to clinical trials in humans and even market approval for a first gene therapy product in Europe. Administration to humans, however, revealed that adaptive immune responses against the vector capsid can present an obstacle to sustained transgene expression due to the activation and expansion of capsid-specific T cells. The limited number of peripheral blood mononuclear cells (PBMCs) obtained from samples within clinical trials allows for little more than monitoring of T-cell responses.
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