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Gottschlich, A.* ; Grünmeier, R.* ; Hoffmann, G.V.* ; Nandi, S.* ; Kavaka, V.* ; Müller, P.J.* ; Jobst, J.* ; Oner, A.* ; Kaiser, R.* ; Gärtig, J.* ; Piseddu, I.* ; Frenz-Wiessner, S.* ; Fairley, S.D.* ; Schulz, H.* ; Igl, V.* ; Janert, T.A.* ; Di Fina, L.* ; Mulkers, M.* ; Thomas, M. ; Briukhovetska, D.* ; Simnica, D.* ; Carlini, E.* ; Tsiverioti, C.A.* ; Trefny, M.P.* ; Lorenzini, T.* ; Märkl, F.* ; Mesquita, P.* ; Brabenec, R. ; Strzalkowski, T.* ; Stock, S.* ; Michaelides, S.* ; Hellmuth, J.C.* ; Thelen, M.* ; Reinke, S.N.* ; Klapper, W.* ; Gelebart, P.F.* ; Nicolai, L.* ; Marr, C. ; Beltrán, E.* ; Megens, R.T.A.* ; Klein, C.* ; Baran-Marszak, F.* ; Rosenwald, A.* ; von Bergwelt-Baildon, M.* ; Bröckelmann, P.J.* ; Endres, S. ; Kobold, S.

Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma.

Blood 145, 1536-1552 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The success of targeted therapies for hematological malignancies has heralded their potential as both salvage treatment and early treatment lines, reducing the need for high-dose, intensive, and often toxic chemotherapeutic regimens. For young patients with classic Hodgkin lymphoma (cHL), immunotherapies provide the possibility to lessen long-term, treatment-related toxicities. However, suitable therapeutic targets are lacking. By integrating single-cell dissection of the tumor landscape and an in-depth, single-cell–based off-tumor antigen prediction, we identify CD86 as a promising therapeutic target in cHL. CD86 is highly expressed on Hodgkin and Reed-Sternberg cancer cells and cHL-specific tumor-associated macrophages. We reveal CD86–CTLA-4 as a key suppressive pathway in cHL, driving T-cell exhaustion. Cellular therapies targeting CD86 had extraordinary efficacy in vitro and in vivo and were safe in immunocompetent mouse models without compromising bacterial host defense in sepsis models. Our results prove the potential value of anti-CD86 immunotherapies for treating cHL.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Tumor Microenvironment; Gene-expression; Phase-ii; Efficacy
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 145, Issue: 14, Pages: 1536-1552 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
Institute of AI for Health (AIH)
Grants LMUexcellent of LMU Munich
Institutional Strategy LMUexcellent of LMU Munich
Ernst Jung Stiftung
Wilhelm Sander-Stiftung
German Cancer Aid (Deutsche Krebshilfe)
Else KronerFresenius-Stiftung
Horizon 2020 program of the European Union
Melanoma Research Alliance
International doctoral program "i-Target: immunotargeting of cancer" - Elite Network of Bavaria
DKTK School of Oncology
Deutsche Forschungsgemeinschaft (DFG)
TANGO
Bavarian Cancer Research Center (BZKF)
Bundesministeriumfr Bildung und Forschung
European Research Council
DFG (German Research Foundation)
Else Krner-Fresenius Clinician Scientist Program Cancer Immunotherapy, the Munich Clinician Scientist Program
Hightech Agenda Bayern
European Research Council under the European Union
German Federal Ministry of Education and Research (BMBF)
Care for Rare Foundation
Novartis Foundation (InCa prize)
Volkswagen Foundation
DFG (German Research Foundation) under Germany's Excellence Strategy
Bavarian Research Foundation
Monika-Kutzner Foundation for Cancer Research
Hector Foundation
Fritz Bender Foundation
DFG
Forderprogramm fuer Forschung und Lehre of the Medical Faculty of the LMU Munich