Technology

CAR-T CELL THERAPY

CAR T-cell therapy makes use of the patients’ own immune system to combat their disease. T-cells are genetically engineered to express a chimeric antigen receptor (CAR) that allows for the detection and destruction of tumor cells. However, currently FDA- and EMA-approved CAR T-cells fail in half of the patients mainly due to the loss of the target antigen, so called antigen escape, as well as the tumor-supporting and immunosuppressive tumor microenvironment (TME).

CXCR5 CAR-T CELLS

Our approach to overcome those main drivers for relapse is the introduction of the chemokine receptor CXCR5 as novel target antigen with high potential to avoid antigen escape. Additionally, CXCR5 is expressed on tumorigenic B-cells and on T- follicular helper (TFH) cells in the TME. This enables a unique dual functionality by tackling the tumor and its supportive microenvironment to achieve deep and long-lasting tumor cell elimination.

Scientific Publications

202520242022202120182015 -REVIEWS
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2025

Targeting MYCN upregulates LACAM tumor antigen in MYCN-dysregulated neuroblastoma to increase CAR T cell efficacy.

Authors

Grunewald L, Andersch L, Helmsauer K, Schwiebert S, Klaus A, Henssen AG, Straka T, Lodrini M, Wicha SG, Fuchs S, Hertwig F, Westermann F, Vitali A, Caramel C, Büchel G, Eilers M, Astrahantseff K, Eggert A, Höpken UE, Schulte JH, Blankenstein T, Anders K, Künkele A

Journal

Pharmacol Res.

Citation

Front Immunol 15: 1383136

DOI

doi:10.1016/j.phrs.2025.107608

Safety, tolerability and early efficacy of mdc-CAR-BCMA001 – a high affinity BCMA targeting CAR T-cell therapy in patients with multiple myeloma and diffuse large B-cell lymphoma

Authors

Jingting Luan, Brigitte Neuber, Carina Wenzel, Malte Von Bonin, Katharina Epp, Raphael Teipel, Jonas Schadt, Angela Hueckelhoven-Krauss, Korinna Jöhrens, Sylvia Herold, Martin Bornhaeuser, Carsten Mueller-Tidow, Anita Schmitt, Armin Rehm, Uta Hoepken, Michael Schmitt, Martin Wermke

Journal

Blood

Citation

Blood (2025) 146 (Supplement 1): 2388.

DOI

doi:10.1182/blood-2025-2388

Bispecific BAFF-R/BCMA CAR T cells control growth of heterogeneous plasma cells in multiple myeloma

Authors

Agnese Fiori, Karin Zimmermann, Anna Li, Jörg Westermann, Ioannis Anagnostopoulos, Lutz Menzel, Mario Bunse, Henry Erdlei, Jeyan Jayarajan, Florian Grünschläger, Juan Pablo Ortiz-Aguirre, Simon Haas, Uwe-Jens Teßmann, Jens Freitag, Andreas Rosenwald, Larry Kwak, Xiuli Wang, Zhenyuan Dong, Soungchul Cha, John Reiser, Eigen Peralta, Bahram Valamehr, Jan Krönke, Uta E. Höpken,Armin Rehm

Journal

Molecular Therapy

DOI

doi:10.1016/j.ymthe.2025.12.005

2024

CXCR4 has a dual role in improving the efficacy of BCMA redirected CAR-NK cells in multiple myeloma.

Authors

Moles MW, Erdlei H, Menzel L, Massaro M, Fiori A, Bunse M, Schrinpf M, Gerlach K, Gudipati V, Reiser J, Mathavan K, Goodrich J, Huppa JB, Kroenke J, Valamehr B, Höpken UE, Rehm A (2024).

Journal

Front Immunol.

DOI

doi:10.3389/fimmu.2024.1383136

CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury.

Authors

Lodka D, Zschummel M, Bunse M, Rousselle A, Sonnemann J, Kettritz R, Höpken UE*, Schreiber A*

Journal

Ann Rheum Dis.

DOI

doi:10.1136/ard-2023-224875

In vitro functionality and endurance of GMP-compliant point-of-care BCMA.CAR-T cells at different timepoints of cryopreservation.

Authors

Jiang G, Neuber B, Hückelhoven-Krauss A, Höpken U, Ding Y, Sedloev D, Wang L, Reichmann A, Eberhardt F, Wermke M, Rehm A, Müller-Tidow A, Schmitt A, Schmitt M

Journal

Int J Mol Sci.

DOI

doi:10.33.90/ijms25031394

2022

Quadruple gene-engineered natural killer cells enable multi-antigen targeting for durable antitumor activity against multiple myeloma.

Authors

Cichocki F, Bjordahl R, Goodridge JP, Mahmood S, Gaidarova S, Abujarour R, Davis ZB, Merino A, Tuininga K, Wang H, Kumar A, Groff B, Witty A, Bonello G, Huffman J, Dailey T, Lee TT, Malmberg K-J, Walcheck B, Höpken U, Rehm A, Valamehr B, Miller JS

Journal

Nature Communications.

DOI

doi:10.1038/s41467-022-35127-2

EBAG9-silencing exerts an immune checkpoint function without aggravating adverse effects.

Authors

Wirges A, Bunse M, Joedicke JJ, Blanc E, Gudipati V, Moles MW, Shiku H, Beule D, Huppa JB, Höpken UE, Rehm A

Journal

Molecular Therapy.

DOI

doi:10.1016/j.ymthe.2022.07.009

EBAG9 controls CD8+ T cell memory formation responding to non-infectious stimuli.

Authors

Rehm A, Wirges A, Hoser D, Fischer C, Herda S, Gerlach K, Sauer S, Willimsky G, Höpken UE

Journal

JCI Insight.

DOI

doi:10.1172/jci.insight.155534

Pharmacological interventions enhance virus-free geenaration of TRAC-replaced CAR T cells.

Authors

Kath J, Weijie D, Pruene A, Braun T, Thommandru B, Turk R, Sturgeon ML, Kurgan GL, Amini L, Stein M, Zittel, Martini S, Ostendorf L, Wilhelm A, Akyüz L, Rehm A, Höpken UE, Pruß A, Künkele A, Jacobi AM, Volk H-D, Schmueck-Heneresse M, Stripecke R, Reinke P, Wagner DL

Journal

Mol Ther Methods Clin Dev.

DOI

doi:10.1016/j.omtm.2022.03.018

Comparison of FACS and PCR for detection of BCMA-CAR-T cells.

Authors

Reichmann A, Kunz A, Joedicke JJ, Höpken UE, Keib A, Neuber B, Sedloev D, Wang L, Jiang G, Hückelhoven-Krauss A, Eberhardt F, Müller-Tidow C, Wermke M, Rehm A, Schmitt M, Schmitt A

Journal

Int. J. Mol. Sci.

DOI

doi:10.3390/ijms23020903

2021

Accelerating clinical scale production of BCMA CAR T cells with defined maturation stages.

Authors

Joedicke JJ, Großkinsky U, Gerlach K, Künkele A, Höpken UE*, Rehm A*

Journal

Mol Ther Methods Clin Dev

DOI

doi:10.1016/j.omtm.2021.12.005

CD28 co-stimulus achieves superior CAR T cell effector function against solid tumors than 4-1BB co-stimulus.

Authors

Textor A, Grunewald L, Anders K, Klaus A, Schwiebert S, Winkler A, Stecklum M, Rolff J, Henssen AG, Höpken UE, Eggert A, Schulte JH, Jensen MC, Blankenstein T, Künkele A

Journal

Cancers

DOI

doi:10.3390/cancers13051050

CXCR5 CAR-T cells simultaneously target B cell Non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells.

Authors

Bunse B, Pfeilschifter J, Bluhm J, Zschummel M, Joedicke JJ, Wirges A, Stark H, Kretschmer V, Chmielewski M, Uckert W, Abken H, Westermann J, Rehm A*, and Höpken UE*

Journal

Nature Communications.

DOI

doi:10.1038/s41467-020-20488-3

2018

CAR T cells with enhanced sensitivity to B cell maturation antigen for the targeting of B cell non-Hodgkin’s lymphoma and multiple myeloma.

Authors

Bluhm J, Kieback E, Marino SF, Oden F, Westermann J, Chmielewski M, Abken H, Uckert W, Höpken UE*, Rehm A*

Journal

Molecular Therapy

DOI

doi:10.1016/j.ymthe.2018.06.012

2015

Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.

DOI

doi:10.1016/j.molonc.2015.03.010

2014

Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation.

DOI

doi:10.1158/2159-8290.CD-14-0096

2010

The homeostatic chemokine receptor CXCR5 is required for mucosa-associated lymphoid neogenesis in chronic Helicobacter pylori-induced inflammation.

DOI

doi:10.1007/s00109-010-0658-6

2009

The tumor-associated antigen EBAG9 negatively regulates the cytolytic capacity of mouse CD8+ T cell.

DOI

doi:10.1172/JCI37760

2007

CXCR5-dependent antigen-specific lymphoid neo-organogenesis in a chronic model of rheumatoid arthritis.

DOI

doi:10.1002/art.22939

2006

Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs.

DOI

doi:10.1182/blood.v99.4.1109

2022

Generation of Redirected Engineered Human Chimeric Antigen Receptor (CAR) T Cells.

DOI

doi:10.1007/978-1-0716-2441-8_4

2020

Angiogenesis in lymph nodes is a critical regulator of immune response and lymphoma growth.

DOI

doi:10.3389/fimmu.2020.591741

2019

Targeting the Tumor Microenvironment of Leukemias and Lymphomas.

DOI

doi:10.1016/j.trecan.2019.05.001

2012

Homeostatic chemokines guide lymphoma cells to tumor growth-promoting niches within secondary lymphoid organs.

DOI

doi:10.1007/s00109-012-0906-z