RESUMEN
HLA-DQA1*05:112 differs from HLA-DQA1*05:05:01:01 by one nucleotide substitution in codon -7 in exon 1.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas alfa de HLA-DQ , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas alfa de HLA-DQ/genética , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Codón , Alineación de SecuenciaRESUMEN
HLA-DRB1*04:379N differs from HLA-DRB1*04:01:01:01 by one nucleotide substitution in codon 4 in exon 1.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas HLA-DRB1/genética , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Codón , Alineación de SecuenciaRESUMEN
HLA-DRB4*01:182 differs from HLA-DRB4*01:03:01:01 by one nucleotide substitution in codon 172 in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB4 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Cadenas HLA-DRB4/genética , Codón , Alineación de SecuenciaRESUMEN
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.
Asunto(s)
Secuencia de Bases , Humanos , Alelos , Cadenas beta de HLA-DQ/genética , IntronesRESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales , Trasplante de Riñón , Humanos , Alelos , Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto , Antígenos HLA , Isoanticuerpos , Riñón , Receptores de TrasplantesRESUMEN
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.
Asunto(s)
Neoplasias Pulmonares , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1 , Biomarcadores de Tumor , Neoplasias/tratamiento farmacológico , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
HLA-A*32:177 differs from HLA-A*32:01:01:01 by one nucleotide substitution in codon -16 in exon 1.
Asunto(s)
Antígenos HLA-A , Nucleótidos , Humanos , Alelos , Exones/genética , Análisis de Secuencia de ADN , Antígenos HLA-A/genéticaRESUMEN
HLA-DPB1*1516:01 differs from HLA-DPB1*1229:01 by seven nucleotide substitutions in exon 3.
Asunto(s)
Secuencia de Bases , Humanos , Alelos , Cadenas beta de HLA-DP/genética , Exones/genéticaRESUMEN
HLA-DPA1*02:122 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 78 in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Humanos , Alelos , Alineación de Secuencia , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genética , Análisis de Secuencia de ADNRESUMEN
HLA-DRB3*02:194 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 78 in exon 2.
Asunto(s)
Secuencia de Bases , Humanos , Cadenas HLA-DRB3/genética , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADN , Cadenas HLA-DRB1RESUMEN
HLA-B*14:122 differs from HLA-B*14:02:01:01 by one nucleotide substitution in codon 102 in exon 3.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Codón , Antígenos HLA-B/genética , Análisis de Secuencia de ADNRESUMEN
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.
Asunto(s)
Inmunoterapia Adoptiva , Neoplasias , Humanos , Inmunoterapia Adoptiva/métodos , Neoplasias/patología , Linfocitos T , Receptores de Antígenos de Linfocitos T , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
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.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/prevención & control , Trasplante Homólogo , Aminoácidos , Alelos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos T , TransgenesRESUMEN
HLA-B*08:312 differs from HLA-B*08:01:01:01 by one nucleotide substitution in codon 324 in exon 6.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADNRESUMEN
HLA-C*16:98:02 differs from HLA-C*16:98:01 by one nucleotide substitution in codon 132 in exon 3.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADNRESUMEN
HLA-DRB1*13:03:13 differs from HLA-DRB1*13:03:01:01 by one nucleotide substitution in codon 180 in exon 3.
Asunto(s)
Cadenas HLA-DRB1 , Humanos , Cadenas HLA-DRB1/genética , Secuencia de Bases , Alelos , Exones/genética , CodónRESUMEN
HLA-B*39:06:09 differs from HLA-B*39:06:02:01 by one nucleotide substitution in codon 135 in exon 3.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Codón , Antígenos HLA-B/genética , Análisis de Secuencia de ADNRESUMEN
HLA-DPA1*01:03:51 differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in codon 146 in exon 3.
Asunto(s)
Cadenas alfa de HLA-DP , Humanos , Alelos , Alineación de Secuencia , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
HLA-DRB1*11:324 differs from HLA-DRB1*11:62:02 by one nucleotide substitution in codon 38 in exon 2.
Asunto(s)
Cadenas HLA-DRB1 , Humanos , Cadenas HLA-DRB1/genética , Secuencia de Bases , Alelos , Exones/genética , CodónRESUMEN
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.