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  1. Article ; Online: Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer.

    Simnica, Donjetë / Kobold, Sebastian

    The New England journal of medicine

    2022  Volume 387, Issue 6, Page(s) 573

    MeSH term(s) Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Genes, T-Cell Receptor ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms
    Chemical Substances Antigens, Neoplasm
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2208623
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.34: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Book ; Online ; Thesis: Identification of T Cell Receptor Repertoire Signatures in Age, Autoimmune Conditions and Cancer using Next-Generation Sequencing

    Simnica, Donjete [Verfasser]

    2020  

    Author's details Donjete Simnica
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
    Publishing place Hamburg
    Document type Book ; Online ; Thesis
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  3. Article ; Online: Subclonal heterogeneity sheds light on the transformation trajectory in IGLV3-21

    Paschold, Lisa / Simnica, Donjete / Brito, Ramon Benitez / Zhang, Tianjiao / Schultheiß, Christoph / Dierks, Christine / Binder, Mascha

    Blood cancer journal

    2022  Volume 12, Issue 3, Page(s) 49

    MeSH term(s) Disease Progression ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Mutation
    Language English
    Publishing date 2022-03-30
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-022-00650-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Targeting the Mutational Landscape of Bystander Cells: Drug-Promoted Blood Cancer From High-Prevalence Pre-neoplasias in Patients on BRAF Inhibitors.

    Simnica, Donjete / Ittrich, Harald / Bockemeyer, Carsten / Stein, Alexander / Binder, Mascha

    Frontiers in oncology

    2020  Volume 10, Page(s) 540030

    Abstract: Drug-promoted cancers are increasingly recognized as a serious clinical problem in patients receiving BRAF inhibitory treatment. Here we report on a patient ... ...

    Abstract Drug-promoted cancers are increasingly recognized as a serious clinical problem in patients receiving BRAF inhibitory treatment. Here we report on a patient with
    Language English
    Publishing date 2020-09-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.540030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Early relapse detection by monitoring of circulating cell-free DNA in patients with localized head and neck squamous cell carcinoma: A subgroup analysis of the multicenter randomized clinical trial IMSTAR-HN.

    Jonas, Hanna / Simnica, Donjete / Bußmann, Lara / Zech, Henrike / Doescher, Johannes / Laban, Simon / Busch, Chia-Jung / Binder, Mascha

    Oral oncology

    2022  Volume 126, Page(s) 105733

    MeSH term(s) Cell-Free Nucleic Acids ; Head and Neck Neoplasms/diagnosis ; Head and Neck Neoplasms/genetics ; Humans ; Neoplasm Recurrence, Local/diagnosis ; Squamous Cell Carcinoma of Head and Neck
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2022-01-29
    Publishing country England
    Document type Letter ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2022.105733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4869: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.A 456: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: PD-L1 Amino Acid Position 88 Represents a Hotspot for PD-L1 Stability With Relevance for PD-L1 Inhibition.

    Claaß, Luise Victoria / Schultheiß, Christoph / Scholz, Rebekka / Paschold, Lisa / Simnica, Donjete / Heinemann, Volker / Stintzing, Sebastian / Binder, Mascha

    Frontiers in oncology

    2022  Volume 12, Page(s) 941666

    Abstract: The two most common antibody targeting principles in oncology are the induction of direct antitumor effects and the release of antitumor T cell immunity by immune checkpoint blockade. These two principles, however, may be overlapping if the targeted ... ...

    Abstract The two most common antibody targeting principles in oncology are the induction of direct antitumor effects and the release of antitumor T cell immunity by immune checkpoint blockade. These two principles, however, may be overlapping if the targeted checkpoint molecule is not located on the immune cell but on the tumor cell itself. Secondary resistance by epitope escape may therefore remain a challenge in both settings. We previously reported epitope escape through L88S and truncating programmed cell death ligand 1 (PD-L1) gene mutations in colorectal cancer patients on selective pressure with avelumab, a PD-L1-directed checkpoint blocker that-in addition to T cell disinhibition-allows direct tumor cell killing
    Language English
    Publishing date 2022-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.941666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Azacitidine-induced reconstitution of the bone marrow T cell repertoire is associated with superior survival in AML patients.

    Grimm, Juliane / Simnica, Donjete / Jäkel, Nadja / Paschold, Lisa / Willscher, Edith / Schulze, Susann / Dierks, Christine / Al-Ali, Haifa Kathrin / Binder, Mascha

    Blood cancer journal

    2022  Volume 12, Issue 1, Page(s) 19

    Abstract: Hypomethylating agents (HMA) like azacitidine are licensed for the treatment of acute myeloid leukemia (AML) patients ineligible for allogeneic hematopoietic stem cell transplantation. Biomarker-driven identification of HMA-responsive patients may ... ...

    Abstract Hypomethylating agents (HMA) like azacitidine are licensed for the treatment of acute myeloid leukemia (AML) patients ineligible for allogeneic hematopoietic stem cell transplantation. Biomarker-driven identification of HMA-responsive patients may facilitate the choice of treatment, especially in the challenging subgroup above 60 years of age. Since HMA possesses immunomodulatory functions that constitute part of their anti-tumor effect, we set out to analyze the bone marrow (BM) immune environment by next-generation sequencing of T cell receptor beta (TRB) repertoires in 51 AML patients treated within the RAS-AZIC trial. Patients with elevated pretreatment T cell diversity (11 out of 41 patients) and those with a boost of TRB richness on day 15 after azacitidine treatment (12 out of 46 patients) had longer event-free and overall survival. Both pretreatment and dynamic BM T cell metrics proved to be better predictors of outcome than other established risk factors. The favorable broadening of the BM T cell space appeared to be driven by antigen since these patients showed significant skewing of TRBV gene usage. Our data suggest that one course of AZA can cause reconstitution to a more physiological T cell BM niche and that the T cell space plays an underestimated prognostic role in AML.Trial registration: DRKS identifier: DRKS00004519.
    MeSH term(s) Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/therapeutic use ; Azacitidine/therapeutic use ; Bone Marrow/drug effects ; Bone Marrow/pathology ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/epidemiology ; Leukemia, Myeloid, Acute/pathology ; Male ; Middle Aged ; Survival Analysis ; T-Lymphocytes/drug effects ; T-Lymphocytes/pathology
    Chemical Substances Antimetabolites, Antineoplastic ; Azacitidine (M801H13NRU)
    Language English
    Publishing date 2022-01-28
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-022-00615-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination.

    Paschold, Lisa / Klee, Bianca / Gottschick, Cornelia / Willscher, Edith / Diexer, Sophie / Schultheiß, Christoph / Simnica, Donjete / Sedding, Daniel / Girndt, Matthias / Gekle, Michael / Mikolajczyk, Rafael / Binder, Mascha

    Frontiers in immunology

    2022  Volume 13, Page(s) 876306

    Abstract: The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody ... ...

    Abstract The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody affinity to the ancestral strain - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants since high affinity may offer some flexibility to compensate for strain-individual mutations. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.
    MeSH term(s) Antibodies, Neutralizing ; Antibodies, Viral ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/metabolism ; Humans ; Pandemics ; SARS-CoV-2/genetics ; Vaccination/methods ; mRNA Vaccines/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; mRNA Vaccines
    Language English
    Publishing date 2022-05-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.876306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Responsiveness to Immune Checkpoint Inhibitors Is Associated With a Peripheral Blood T-Cell Signature in Metastatic Castration-Resistant Prostate Cancer.

    Simnica, Donjete / Smits, Minke / Willscher, Edith / Fanchi, Lorenzo F / Kloots, Iris S H / van Oort, Inge / Gerritsen, Winald / Mehra, Niven / Binder, Mascha

    JCO precision oncology

    2022  Volume 4, Page(s) 1374–1385

    Abstract: Purpose: Although most patients with microsatellite instable (MSI) metastatic castration-resistant prostate cancer (mCRPC) respond to immune checkpoint blockade (ICB), only a small subset of patients with microsatellite stable (MSS) tumors have similar ... ...

    Abstract Purpose: Although most patients with microsatellite instable (MSI) metastatic castration-resistant prostate cancer (mCRPC) respond to immune checkpoint blockade (ICB), only a small subset of patients with microsatellite stable (MSS) tumors have similar benefit. Biomarkers defining ICB-susceptible subsets of patients with MSS mCRPC are urgently needed.
    Methods: Using next-generation T-cell repertoire sequencing, we explored immune signatures in 54 patients with MSS and MSI mCRPC who were treated with or without ICB. We defined subset-specific immune metrics as well as T-cell clusters and correlated the signatures with treatment benefit.
    Results: Consistent overlaps between tumor and peripheral T-cell repertoires suggested that blood was an informative material to identify relevant T-cell signatures. We found considerably higher blood T-cell richness and diversity and more shared T-cell clusters with low generation probability (pGen) in MSI versus MSS mCRPC, potentially reflecting more complex T-cell responses because of a greater neoepitope load in the MSI subset. Interestingly, patients with MSS mCRPC with shared low pGen T-cell clusters showed significantly better outcomes with ICB, but not with other treatments, compared with patients without such clusters. Blood clearance of T-cell clusters on ICB treatment initiation seemed to be compatible with T-cell migration to the primary tumor or metastatic sites during the process of clonal replacement as described for other tumors receiving ICB.
    Conclusion: The MSI mCRPC subset shows a distinct T-cell signature that can be detected in blood. This signature points to immune parameters that could help identify a subset of patients with MSS mCRPC who may have an increased likelihood of responding to ICB or to combination approaches including ICB.
    Language English
    Publishing date 2022-01-20
    Publishing country United States
    Document type Journal Article
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.20.00209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination.

    Ellingsen, Espen Basmo / Bounova, Gergana / Kerzeli, Iliana / Anzar, Irantzu / Simnica, Donjete / Aamdal, Elin / Guren, Tormod / Clancy, Trevor / Mezheyeuski, Artur / Inderberg, Else Marit / Mangsbo, Sara M / Binder, Mascha / Hovig, Eivind / Gaudernack, Gustav

    Journal of translational medicine

    2022  Volume 20, Issue 1, Page(s) 419

    Abstract: Background: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue ... ...

    Abstract Background: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment.
    Methods: The trial was an open-label, single-center phase I/IIa study. Eligible patients had unresectable metastatic melanoma. Patients received up to 9 UV1 vaccinations and four ipilimumab infusions. Clinical responses were assessed according to RECIST 1.1. Patients were followed up for progression-free survival (PFS) and overall survival (OS). Whole-exome and RNA sequencing, and multiplex immunofluorescence were performed on the biopsies. T cell receptor (TCR) sequencing was performed on the peripheral blood and tumor tissues.
    Results: Twelve patients were enrolled in the study. Vaccine-specific immune responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-γ gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-γ gene signature was detected in clinically responding patients.
    Conclusion: Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors. Trial registration Clinicaltrials.gov identifier: NCT02275416. Registered October 27, 2014. https://clinicaltrials.gov/ct2/show/NCT02275416?term=uv1&draw=2&rank=6.
    MeSH term(s) Humans ; Ipilimumab/pharmacology ; Ipilimumab/therapeutic use ; Melanoma/pathology ; Telomerase ; Tumor Microenvironment ; Vaccination
    Chemical Substances Ipilimumab ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2022-09-11
    Publishing country England
    Document type Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/s12967-022-03624-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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