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T-lymphocyte cell therapy

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T-lymphocyte cell therapy	1

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4⁺ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8⁺ α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4⁺ T-cells and gluten-triggered peripheral blood CD8⁺ T-cells. We show, that in addition to TCRs from gluten-specific CD4⁺ T-cells, TCRs of gluten-triggered CD8⁺ T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8⁺ T-cells were even more expanded in patients than TCRs from gluten-specific CD4⁺ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

01 Feb 2022·European Journal of CancerQ1 · MEDICINE

Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer—findings from the RIBECCA trial

Q1 · MEDICINE

Article

Author: Lüftner, Diana ; Brucker, Sara ; Schaper, Sigrid ; Na, Il-Kang ; Schuler, Martin ; Peuker, Caroline A ; Busse, Antonia ; Grunert, Corinna ; Keilholz, Luisa ; Gjerga, Enio ; Kümmel, Sherko ; Fehm, Tanja ; Keller, Ulrich ; Yaghobramzi, Sarvenaz ; Schneeweiss, Andreas ; Decker, Thomas ; Fasching, Peter ; Janni, Wolfgang ; Hennig, Steffen

BACKGROUNDInhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6i) have significantly improved clinical outcomes in patients with advanced hormone receptor-positive (HR+) breast cancer and have demonstrated favourable antitumour immune responses in preclinical studies.METHODSHere, we investigated peripheral immune responses to ribociclib in patients with metastatic HR+ breast cancer as a preplanned exploratory subanalysis of the RIBECCA trial (NCT03096847). Peripheral blood mononuclear cells were subjected to immune cell profiling, gene expression analysis of immune-related signatures, and deep T cell receptor profiling before treatment started and after 12 weeks of treatment with ribociclib.RESULTSGene expression analysis revealed an upregulation of signatures associated with an activated adaptive immune system and a decrease in immunosuppressive cytokine signalling during treatment with ribociclib. Profiling of peripheral immune cell subpopulations showed a decrease in Treg cell frequencies, which was associated with treatment response. Furthermore, induction of CD4+ naive T cells could be seen, whereas effector and memory T cell populations remained largely unchanged. Correspondingly, T cell repertoire diversity remained mostly unchanged during treatment, although an increase in clonality could be observed in single patients.CONCLUSIONSWe show that treatment with ribociclib has significant effects on the peripheral innate and adaptive immune response in patients with HR+ breast cancer. Our data suggest that these effects lead to an activation of an already existing immune response rather than a de novo induction and make a strong case for future combination strategies of CDK4/6i with immunotherapies to enhance the adaptive immune response in HR+ breast cancer.

01 Mar 2018·Pneumologie

Tumorreaktive T-Zellen als Therapiemöglichkeit beim Lungenkarzinom

Author: Schimek, M ; Eggeling, S ; Hennig, S ; Späth-Schwalbe, E ; Seitz, V

100 Deals associated with HS Diagnomics GmbH

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100 Translational Medicine associated with HS Diagnomics GmbH

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Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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