CTLA4/PD1 blockade; Vaccine; T cells; Immunotherapy; Melanoma
Fässler Mirjam, Diem Stefan, Mangana Joanna, Hasan Ali Omar, Berner Fiamma, Bomze David, Ring Sandra, Niederer Rebekka, del Carmen Gil Cruz Cristina, Pérez Shibayama Christian Ivan, Krolik Michal, Siano Marco, Joerger Markus, Recher Mike, Risch Lorenz, Güsewell Sabine, Risch Martin, Speiser Daniel E., Ludewig Burkhard, Levesque Mitchell P., Dummer Reinhard, Flatz Lukas (2019), Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients, in Journal for ImmunoTherapy of Cancer
, 7(1), 50-50.
Gil-Cruz Cristina, Perez-Shibayama Christian, De Martin Angelina, Ronchi Francesca, van der Borght Katrien, Niederer Rebekka, Onder Lucas, Lütge Mechthild, Novkovic Mario, Nindl Veronika, Ramos Gustavo, Arnoldini Markus, Slack Emma M.C., Boivin-Jahns Valérie, Jahns Roland, Wyss Madeleine, Mooser Catherine, Lambrecht Bart N., Maeder Micha T., Rickli Hans, Flatz Lukas, Eriksson Urs, Geuking Markus B., McCoy Kathy D., et al. (2019), Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy, in Science
, 366(6467), 881-886.
Bomze David, Hasan Ali Omar, Bate Andrew, Flatz Lukas (2019), Association Between Immune-Related Adverse Events During Anti–PD-1 Therapy and Tumor Mutational Burden, in JAMA Oncology
, 5(11), 1633-1633.
Ali Omar Hasan, Bomze David, Ring Sandra, Berner Fiamma, Fässler Mirjam, Diem Stefan, Abdou Marie-Therese, Hammers Christoph, Emtenani Shirin, Braun Anne, Cozzio Antonio, Mani Bernhard, Jochum Wolfram, Schmidt Enno, Zillikens Detlef, Sadik Christian D., Flatz Lukas (2019), BP180-specific IgG is associated with skin adverse events, therapy response and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors, in Journal of the American Academy of Dermatology
Berner Fiamma, Bomze David, Diem Stefan, Ali Omar Hasan, Fässler Mirjam, Ring Sandra, Niederer Rebekka, Ackermann Christoph J., Baumgaertner Petra, Pikor Natalia, Cruz Cristina Gil, van de Veen Willem, Akdis Mübeccel, Nikolaev Sergey, Läubli Heinz, Zippelius Alfred, Hartmann Fabienne, Cheng Hung-Wei, Hönger Gideon, Recher Mike, Goldman Jonathan, Cozzio Antonio, Früh Martin, Neefjes Jacques, et al. (2019), Association of Checkpoint Inhibitor–Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non–Small Cell Lung Cancer, in JAMA Oncology
, 5(7), 1043-1043.
Diem Stefan, Hasan Ali Omar, Ackermann Christoph J, Bomze David, Koelzer Viktor H, Jochum Wolfram, Speiser Daniel E, Mertz Kirsten D, Flatz Lukas (2018), Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease., in Cancer immunology, immunotherapy : CII
, 67(1), 39-45.
Diem Stefan, Schmid Sabine, Krapf Mirjam, Flatz Lukas, Born Diana, Jochum Wolfram, Templeton Arnoud J, Früh Martin (2017), Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab., in Lung cancer (Amsterdam, Netherlands)
, 111, 176-181.
Remy Melissa M, Sahin Mehmet, Flatz Lukas, Regen Tommy, Xu Lifen, Kreutzfeldt Mario, Fallet Benedict, Doras Camille, Rieger Toni, Bestmann Lukas, Hanisch Uwe-Karsten, Kaufmann Beat A, Merkler Doron, Pinschewer Daniel D (2017), Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever., in Cell host & microbe
, 22(3), 354-365.
Kalkavan Halime, Sharma Piyush, Kasper Stefan, Helfrich Iris, Pandyra Aleksandra A, Gassa Asmae, Virchow Isabel, Flatz Lukas, Brandenburg Tim, Namineni Sukumar, Heikenwalder Mathias, Höchst Bastian, Knolle Percy A, Wollmann Guido, von Laer Dorothee, Drexler Ingo, Rathbun Jessica, Cannon Paula M, Scheu Stefanie, Bauer Jens, Chauhan Jagat, Häussinger Dieter, Willimsky Gerald, Löhning Max, Schadendorf Dirk, Brandau Sven, Schuler Martin, Lang Philipp A, Lang Karl S (2017), Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression., in Nature communications
, 8, 14447-14447.
Lukas Flatz, Omar Hasan Ali, Stefan Diem, Wolfram Jochum, Katrin Kerl, Lars French, Eva Markert (2016), Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer., in OncoImmunology
Sandra Ring, Lukas Flatz (2016), Generation of Lymphocytic Choriomeningitis Virus Based Vaccine Vectors., in Sunil Thomas (ed.), Springer, Berlin, 351.
Stefan Diem, Fabienne Keller, Reinhard Rüesch, Samia Maillard, Daniel Speiser, Reinhard Dummer, Marco Siano, Simone Goldinger, Ursula Urner-Bloch, Lukas Flatz (2016), Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy?, in Journal of Immunotherapy
The growing incidence of melanoma is an increasing threat, and effective treatment options for advanced forms of melanoma are scarce. Although recently approved targeted- and immunotherapies have shown objective beneficial effects in metastatic melanoma, in most cases the disease still relapses. In this project we are interested to understand the differences of immune responses against on one side vaccine vector intrinsic epitopes compared to tumor associated antigens consisting of classical melanoma antigens (melanA, gp100, trp2) and also recently characterized neoepitopes (emerged through de novo mutations in rapidly evolving tumor cells) - all provided by the same vaccine. These antigens will be presented in the context of the non-propagating recombinant lymphocytic choriomeningitis or adenovirus based vaccine vectors. For both of them we have well described Db restricted epitopes: FQPQNGQFI (NP396), FALSNAEDL (dbp43) respectively. In order to further increase the potency of the T cell immune response we will combine these with prime-boost immunizations using DNA plasmid, vaccinia virus, listeria vaccine vectors against the same antigens. Specifically we will pursue the following goals:1) To understand the topographic distribution and quality of simultaneously vaccine-induced T cells against auto-, neo- and foreign antigens in different immune compartments (skin, lymph nodes, blood, and spleen) in relation to the route of immunization over time.2) To characterize the behavior of anti-tumor and anti-virus T cells after tumor respectively virus challenge not only in the immune compartments but also in the tumor and its microenvironment using classical immunological assays and single cell real-time PCR.3) To unravel the effect of currently used immune activators (CTLA-4 and PD-1 blocking antibodies) on tumor and virus (EBV, CMV, Influenza) specific T cells in patients.A completion of these experiments may stimulate a discussion on thinking of a paradigm change in terms of prophylactic melanoma vaccination in high-risk individuals (Breslow >2mm and positive sentinel lymph node) instead of therapeutic immunotherapy in end stage melanoma.