ABSTRACT
HLA-DQB1*02:01:01:21Q differs from HLA-DQB1*02:01:01:01 by one nucleotide substitution in the splice site in the beginning of intron 3.
Subject(s)
Base Sequence , Humans , Alleles , HLA-DQ beta-Chains/genetics , IntronsABSTRACT
We report data on six kidney or heart recipients who were administered daratumumab to treat or prevent antibody-mediated rejection (ABMR). To date, data are scarce concerning the use of daratumumab in solid organ transplantation and most reports show a decrease in donor-specific antigen (DSA) levels and an improvement in ABMR using a multiple myeloma daratumumab administration scheme, that is, with sequential systematic administration. Here, we report on the efficacy of daratumumab 1/ in reducing the histological signs of ABMR, 2/ in reducing the ability of DSA to bind to donor cells in vitro through negativation of flow cytometry crossmatching, 3/ in preferentially being directed towards antibodies sharing epitopes, suggesting that daratumumab may specifically target activated plasma cells, 4/ and when administered as a single dose. This last point suggests, for the first time, that, as for rituximab in auto-immune diseases, the scheme for daratumumab administration could be different for targeting DSA-producing plasma cells than for tumour cells.
Subject(s)
Antibodies, Monoclonal , Kidney Transplantation , Humans , Alleles , Antibodies, Monoclonal/therapeutic use , Graft Rejection , HLA Antigens , Isoantibodies , Kidney , Transplant RecipientsABSTRACT
Immune checkpoint inhibitors (ICI) have recently become the standard of care for many metastatic solid tumors, with considerable improvements in patient prognosis. However, a non-negligible proportion of patients does not respond to this type of treatment, making it essential to identify predictive factors of this response in order to better adapt the therapy. Among the biomarkers that have been most extensively studied in recent years, tumor PD-L1 levels come out on top, with controversial results for predicting response to ICI. The determination of circulating PD-L1 (or soluble PD-L1) in peripheral blood seems to be an interesting emerging biomarker. Indeed, several studies have investigated its prognostic value, and/or its potential predictive value of response to immunotherapy, and it would appear that there is a correlation between the level of soluble PD-L1 and the level of tumor aggressiveness and therefore prognosis. Furthermore, the results suggest that higher PD-L1 levels are associated with a poorer response to immunotherapy, although this remains to be confirmed in large-scale studies.
Subject(s)
Lung Neoplasms , Neoplasms , Humans , Immune Checkpoint Inhibitors/therapeutic use , B7-H1 Antigen , Biomarkers, Tumor , Neoplasms/drug therapy , Prognosis , Lung Neoplasms/drug therapyABSTRACT
HLA-A*32:177 differs from HLA-A*32:01:01:01 by one nucleotide substitution in codon -16 in exon 1.
Subject(s)
HLA-A Antigens , Nucleotides , Humans , Alleles , Exons/genetics , Sequence Analysis, DNA , HLA-A Antigens/geneticsABSTRACT
HLA-DPB1*1516:01 differs from HLA-DPB1*1229:01 by seven nucleotide substitutions in exon 3.
Subject(s)
Base Sequence , Humans , Alleles , HLA-DP beta-Chains/genetics , Exons/geneticsABSTRACT
HLA-DPA1*02:122 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 78 in exon 2.
Subject(s)
HLA-DP alpha-Chains , Humans , Alleles , Sequence Alignment , Histocompatibility Testing , HLA-DP alpha-Chains/genetics , Sequence Analysis, DNAABSTRACT
HLA-DRB3*02:194 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 78 in exon 2.
Subject(s)
Base Sequence , Humans , HLA-DRB3 Chains/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNA , HLA-DRB1 ChainsABSTRACT
HLA-B*14:122 differs from HLA-B*14:02:01:01 by one nucleotide substitution in codon 102 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
Loss of heterozygosity or HLA loss is a genomic-type escape mechanism highlighted in certain types of relapses after allogeneic hematopoietic stem cell transplantation with a non-HLA identical donor, and especially after haplo-identical transplantation. The diagnosis must be made with certainty because the result conditions the therapy. In this article, the different mechanisms and techniques that can be used for the diagnosis of loss of heterozygosity, as well as the therapeutic options are reviewed, making it possible to establish clinico-biological recommendations for the diagnosis confirmation and management of the patients in relapse.
Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Humans , Societies, Medical , RecurrenceABSTRACT
HLA-C*16:98:02 differs from HLA-C*16:98:01 by one nucleotide substitution in codon 132 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNAABSTRACT
HLA-DRB1*13:03:13 differs from HLA-DRB1*13:03:01:01 by one nucleotide substitution in codon 180 in exon 3.
Subject(s)
HLA-DRB1 Chains , Humans , HLA-DRB1 Chains/genetics , Base Sequence , Alleles , Exons/genetics , CodonABSTRACT
HLA-B*39:06:09 differs from HLA-B*39:06:02:01 by one nucleotide substitution in codon 135 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-DPA1*01:03:51 differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in codon 146 in exon 3.
Subject(s)
HLA-DP alpha-Chains , Humans , Alleles , Sequence Alignment , Histocompatibility Testing , HLA-DP alpha-Chains/geneticsABSTRACT
HLA-DRB1*11:324 differs from HLA-DRB1*11:62:02 by one nucleotide substitution in codon 38 in exon 2.
Subject(s)
HLA-DRB1 Chains , Humans , HLA-DRB1 Chains/genetics , Base Sequence , Alleles , Exons/genetics , CodonABSTRACT
HLA-B*08:312 differs from HLA-B*08:01:01:01 by one nucleotide substitution in codon 324 in exon 6.
Subject(s)
HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNAABSTRACT
In solid tumors, three main complementary approaches of adoptive T-cell therapies were successively developed: tumor-infiltrating lymphocytes, chimeric antigen receptor engineered T cells, and high-affinity T-cell receptor engineered T cells. In this review, we summarized rational and main results of these three adoptive T-cell therapies in solid tumors field and gave an overview of encouraging data and their limits. Then, we listed the major remaining challenges (including tumor antigen loss, on-target/off-tumor effect, tumor access difficulties and general/local immunosubversion) and their lines of research. Finally, we gave insight into the ongoing trials in solid tumor.
Subject(s)
Immunotherapy, Adoptive , Neoplasms , Humans , Immunotherapy, Adoptive/methods , Neoplasms/pathology , T-Lymphocytes , Receptors, Antigen, T-Cell , Cell- and Tissue-Based TherapyABSTRACT
T cell therapy strategies, from allogeneic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remains sometimes to be improved. It therefore appears important to provide a flexible and easily reversible gene expression regulation system to control T cells activity. We developed a gene expression regulation technology that exploits the physiological GCN2-ATF4 pathway's ability to induce gene expression in T cells in response to one essential amino acid deficiency. We first demonstrated the functionality of NUTRIREG in human T cells by transient expression of reporter genes. We then validated that NUTRIREG can be used in human T cells to transiently express a therapeutic gene such as IL-10. Overall, our results represent a solid basis for the promising use of NUTRIREG to regulate transgene expression in human T cells in a reversible way, and more generally for numerous preventive or curative therapeutic possibilities in cellular immunotherapy strategies.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Graft vs Host Disease/prevention & control , Transplantation, Homologous , Amino Acids , Alleles , Hematopoietic Stem Cell Transplantation/adverse effects , T-Lymphocytes , TransgenesABSTRACT
The impact of immunosuppressive therapy (IS) strategies after kidney transplant failure (KTF) on potential future new grafts is poorly established. We assessed the potential benefit of calcineurin inhibitor (CNI)-based IS maintenance throughout the dialysis period on the outcome of the second kidney transplant (KT). We identified 407 patients who underwent a second KT between January 2008 and December 2018 at four French KT centers. Inverse probability of treatment weighting was used to control for potential confounding. We included 205 patients with similar baseline characteristics at KTF: a total of 53 received at least CNIs on the retransplant day (G-CNI), and 152 did not receive any IS (G-STOP). On the retransplant date, G-STOP patients experienced a longer pretransplant dialysis time, were more often hyperimmunized, and underwent more expanded-criteria donor KTs than G-CNI patients. During the second KT follow-up period, rejection episodes were similar in both groups. The 10-year survival rates without death and dialysis were 98.7% and 59.5% in G-CNI and G-STOP patients, respectively. In the multivariable analysis, CNI-based IS maintenance was associated with better survival (hazard ratio: 0.08; 95% confidence interval: 0.01-0.58, p = 0.01). CNI-based IS maintenance throughout the dialysis period after KTF may improve retransplantation outcomes.
Subject(s)
Kidney Diseases , Kidney Transplantation , Humans , Calcineurin Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Propensity Score , Graft Rejection/prevention & control , Renal Dialysis , Kidney , Immunosuppression Therapy , Graft SurvivalABSTRACT
HLA-B*51:384 differs from HLA-B*51:01:01:01 by one nucleotide substitution in codon 267 in exon 4.
Subject(s)
HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-DRB3*02:193 differs from DRB3*02:02:01:11 by one nucleotide substitution in exon 1, and intronic changes.