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Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
Effective antitumor immunity is usually dependent on T-cell-mediated responses. Two kinds of signals are required for the activation of T cells. As described above, the first signal is the antigen-specific binding of a peptide antigen-MHC complex on the surface of antigen presenting cells with antigen specific T-cell receptors. This interaction is necessary but not sufficient to induce primary T-cell activation and production of essential cytokines such as IL-2. It is hypothesized that the presence of this first signal alone may induce a state of readiness to respond to the second signal, known as costimulation. The second signal is transmitted by the antigen-independent binding of costimulatory molecules on APC with their corresponding receptors on T-cells. This signal is required to induce primary T-cell proliferation and other effector functions of the immune response. Without this second signal, the binding of antigen with TCR alone may cause prolonged unresponsiveness or specific T-cell anergy. A number of molecules have been found to mediate this second signal, including the B7 family (unrelated to the HLA-B7 class I molecule described above), which interact with the CD28 receptor on T cells (8,9). B7 is expressed on activated B cells, macrophages, and dendritic cells and is the ligand for CD28 and CTLA-4 on T-cells (10,11).
Clinical and Immunologic Responses to Gene Transfer of an Allogeneic Major Histocompatibility Complex Antigen
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Alison T. Stopeck, Evan M. Hersh
High gene transfer efficiencies were documented in all patients (Table 1). Persistence of the plasmid DNA by PCR or RT-PCR was documented up to 8 weeks (last biopsy obtained) after gene injection. As the number of transfected tumor cells was difficult to estimate by immunohistochemistry, tumor biopsies were also processed into single cell suspensions for flow cytometric analysis. The range and mean number of cells staining positive for HLA-B7 in tumor biopsies pre-gene injection was 0-7%, and 1.27±2.07%, respectively. Thus, tumors were considered positive for HIA-B7 expression if greater than 7% of the cells isolated from biopsies post gene injection expressed HLA-B7 by flow cytometry. In post-therapy biopsies considered positive for HLA-B7 by this definition, 8-30% (mean 15%) of the cells expressed HLA-B7 protein. Immunohistochemical staining confirmed that HLA-B7 was being expressed by tumor cells (Figures 2B, 3C). Increased numbers of tumor infiltrating Τ lymphocytes (TIL) were also observed in several tumor biopsies post gene therapy (Figures 2D, 3D). Generation of specific CTLs against target cells expressing HLA-B7 was analyzed in vitro from patient peripheral blood mononuclear cells before and after therapy. Fourteen of forty-five patients (31%) had an increased frequency of anti-HLA-B7 CTLs in their peripheral blood post-gene injection. Significant changes in NK or LAK cell frequencies before and after treatment were not observed at the time points analyzed.
Uveitis
Published in Mostafa Khalil, Omar Kouli, The Duke Elder Exam of Ophthalmology, 2019
Mostafa Khalil, Omar Kouli, Obaid Kousha
This clinical presentation occurs due to Histoplasma capsulatum (dimorphic fungi). Associated with HLA-B7 and HLA-DR2. Famously occurs in Ohio, Mississippi, and St Lawrence River valleys. More common in patients with AIDS.
Individualized management of cytomegalovirus in solid organ transplant recipients
Published in Expert Review of Precision Medicine and Drug Development, 2021
Huma Saeed, Matthew Thoendel, Raymund R Razonable
Allograft recipients with human leukocyte antigen (HLA)-B7 positive donors and those with HLA B44 alleles are at an increased risk of CMV infection and disease [52,53]. Genetic polymorphisms in certain host genes such as programmed death-1.3 A allele confers increased risk of CMV infection in renal transplant recipients who are not receiving antiviral prophylaxis [54]. Additionally, studies have demonstrated genetic polymorphisms in the newly described Type-III interferons, IFN-λ and IFNL, especially IFNL3 and IFNL4 impact the replication of various viruses, including CMV, due to its direct effect on innate and adaptive immunity as well as direct antiviral functions [55]. A higher incidence of CMV replication has been reported in hosts carrying polymorphism in the IFNL3/4 region, especially among those who were not receiving antiviral prophylaxis [56].
Intralesional therapy as a treatment for locoregionally metastatic melanoma
Published in Expert Review of Anticancer Therapy, 2018
John T. Miura, Jonathan S. Zager
Considered an immunotherapy, Allovectin-7 is an intralesional plasmid that contains DNA sequences encoding human leukocyte antigen (HLA)-B7 and β2 microglobulin, a component of MHC-I [32]. In cancer, one proposed mechanism for disease progression is the alteration of MHC-I, which enables tumor cells to elude the immune response [33]. Allovectin-7 promotes an immune response through the upregulation of MHC-I molecules, resulting in an increase in the frequency of HLA-B27-Cytotoxic T cells, and subsequent pro-inflammatory response [32]. As such, melanoma cells injected with this agent attract T cells and macrophages, which ultimately recognize and destroy injected and non-injected lesions.
HLA and amyotrophic lateral sclerosis: a systematic review and meta-analysis
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023
R. J. Nona, J. M. Greer, R. D. Henderson, P. A. McCombe
Some of the individual studies reported significant associations of HLA serotypes with ALS, including increased HLA-A3 (22,23), HLA-B16 (23), and decreased HLA-B7 (26). The one study that reported on HLA-DR serotypes found a decreased frequency of HLA-DR4 in ALS compared to controls, which was significant prior to correction for multiple comparisons (28). There were also non-significant trends of increased HLA-A2 (21), HLA-A28 (21), HLA-B7 (22), and HLA-B35 (24,25) and decreased HLA-A9 (25). One study showed no significant differences or trends in HLA serotypes in ALS subjects compared to controls (31).