109 research outputs found
Evaluation of high-throughput genomic assays for the Fc gamma receptor locus
Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics
Obinutuzumab versus Rituximab in young patients with advanced DLBCL, a PET-guided and randomized phase 3 study by LYSA.
Rituximab plus polychemotherapy is standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED trial
compares obinutuzumab to rituximab. GAINED (NCT01659099) is an open-label, randomized phase 3 trial.
Transplant-eligible patients (18-60yrs) with untreated aged-adjusted international prognostic index (aaIPI) ≥1
DLBCL were randomized (1:1) between obinutuzumab or rituximab. Patients were stratified by aaIPI (1; 2-3)
and chemotherapy regimen (ACVBP; CHOP). Consolidation treatment was determined according to response
assessed by centrally reviewed interim semi-quantitative PET. Responders after cycle 2 and 4 (PET2-/PET4-)
received planned immuno-chemotherapy consolidation. Responders only after cycle 4 (PET2+/4-) received highdose methotrexate plus transplantation. The primary objective was an 8% improvement (HR=0.73; 80% power;
alpha risk 2.5%; one-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. Events included death,
progression, PET 2 or 4 positivity, modification of planned treatment. From September 20, 2012, 670 patients
were enrolled (obinutuzumab n=336; rituximab n=334). 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received
CHOP and 324 (48.4%) received ACVBP. Median follow-up was 38.7 months. The 2-year EFS were similar in
obinutuzumab and rituximab groups (59.8% vs 56.6%; p=0.123; HR=0.88). The 2-year PFS in the whole cohort
was 83.1% (95%CI 80–85.8). PET2-/4- and PET2+/4- had similar 2-year PFS and OS (89.9% vs 83.9%) and
94.8% vs 92.8%). The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were
more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in untreated
aaIPI≥1 DLBCL transplant-eligible patients
Transcriptional response of Atlantic salmon families to Piscirickettsia salmonis infection highlights the relevance of the iron-deprivation defence system
The members of the RH gene family (RH50 and RH30) followed different evolutionary pathways
The preparation, characterization, and application of environment-friendly monoclonal antibodies for human blood cell
A unique gene encodes spliceoforms of the B-cell adhesion molecule cell surface glycoprotein of epithelial cancer and of the Lutheran blood group glycoprotein
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