We report the safety and tolerability of 87 infusions of lentiviral vector–modified autologous CD4 T cells (VRX496-T; trade name, Lexgenleucel-T) in 17 HIV patients with well-controlled viremia. Antiviral effects were studied during analytic treatment interruption in a subset of 13 patients. VRX496-T was associated with a decrease in viral load set points in 6 of 8 subjects (P = .08). In addition, A → G transitions were enriched in HIV sequences after infusion, which is consistent with a model in which transduced CD4 T cells exert antisense-mediated genetic pressure on HIV during infection. Engraftment of vector-modified CD4 T cells was measured in gut-associated lymphoid tissue and was correlated with engraftment in blood. The engraftment half-life in the blood was approximately 5 weeks, with stable persistence in some patients for up to 5 years. Conditional replication of VRX496 was detected periodically through 1 year after infusion. No evidence of clonal selection of lentiviral vector–transduced T cells or integration enrichment near oncogenes was detected. This is the first demonstration that gene-modified cells can exert genetic pressure on HIV. We conclude that gene-modified T cells have the potential to decrease the fitness of HIV-1 and conditionally replicative lentiviral vectors have a promising safety profile in T cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587318 | PMC |
| http://dx.doi.org/10.1182/blood-2012-07-447250 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.
Proc Natl Acad Sci U S A
January 2025
Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.
View Article and Find Full Text PDFCirculating PD-1hi CXCR5- and CXCR5+ CD4 T cells are elevated in patients with newly diagnosed Giant Cell Arteritis and predict relapse.
Rheumatology (Oxford)
January 2025
Department of Rheumatology, Hospital Universitario La Paz-IdiPaz, Madrid, Spain.
Objectives: Giant cell arteritis (GCA) is a large/medium-vessel granulomatous vasculitis, and the PD-1/PD-L1 coinhibitory pathway seems to be implicated in its pathogenesis. CD4 T cells expressing high PD-1 levels, CD4+CXCR5-PD-1hi peripheral helper (Tph) and CD4+CXCR5+PD-1hi follicular helper T cells (Tfh), are key mediators of autoimmunity. Their frequencies are elevated in the peripheral blood of subjects with several autoimmune conditions but have not been investigated in GCA.
View Article and Find Full Text PDFDefective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth.
Cell Rep
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.
View Article and Find Full Text PDFUnsupervised clustering reveals noncanonical myeloid cell subsets in the brain tumor microenvironment.
Cancer Immunol Immunother
January 2025
Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
The tumor immune microenvironment (TiME) of human central nervous system (CNS) tumors remains to be comprehensively deciphered. Here, we employed flow cytometry and RNA sequencing analysis for a deep data-driven dissection of a diverse TiME and to uncover noncanonical immune cell types in human CNS tumors by using seven tumors from five patients. Myeloid subsets comprised classical microglia, monocyte-derived macrophages, neutrophils, and two noncanonical myeloid subsets: CD3 myeloids and CD19 myeloids.
View Article and Find Full Text PDFA retrospective analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation for transfusion-dependent β-thalassemia: focus on T and B lymphocyte reconstitution.
Ann Hematol
January 2025
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
Background: Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often refractory and relapsing, leading to increased mortality post-HSCT.
Methods: We retrospectively analyzed the cases of patients with transfusion-dependent β-thalassemia (TDT) who underwent allo-HSCT to study their clinical features, the occurrence of AIHA post-HSCT, and treatment response and to explore the possible pathogenesis of AIHA.
Result: A total of 113 patients were registered in the study, out of whom 14 developed AIHA following allo-HSCT, resulting in a cumulative incidence of 12.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!