M11‐CAR T cells inhibit murine cytomegalovirus in vitro upon recognition of virion‐ and cell‐associated glycoprotein B
6 affiliations
- 1Harald zur Hausen Institute of Virology University Hospital Erlangen, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
- 2Present address: C Garçon, Bavarian Nordic A/S Planegg Germany
- 3Present address: H Menschikowski, BG Trauma Centre Tübingen Eberhard Karls University Tübingen Tübingen Germany
- 4Present address: L Bauer, Max Planck Centre for Physics and Medicine Erlangen Germany
- 5Bioinformatics, Institute of Biochemistry Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
- 6Chair of Genetics Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
Abstract
Objectives: Viral infections are predominantly managed with conventional antiviral drugs, which, despite their efficacy, can cause toxicity and promote resistance. Cell‐based immunotherapies offer an alternative, but cytomegaloviruses (CMV) profoundly interfere with MHC class I antigen presentation, thereby impairing conventional virus‐specific T‐cell responses towards infected cells. We therefore aimed to develop an MHC‐unrestricted CAR T‐cell approach for CMV infection and investigate its antiviral activity.
Methods: We generated M11‐CAR, a fully murine, second‐generation CAR based on the M11 monoclonal antibody targeting glycoprotein B (gB) of murine CMV (MCMV). Primary splenocytes were transduced to assess CAR functionality following ectopic gB expression or MCMV infection. T‐cell cytotoxicity, cytokine production and antiviral activity were evaluated and compared with human CD19‐specific control CAR T cells.
Results: M11‐CAR T cells specifically recognized gB following ectopic expression and MCMV infection, inducing cytotoxicity and cytokine production. CAR‐mediated cytokine production, particularly interferon‐γ, translated into robust MCMV inhibition. Increasing MCMV loads impaired cytokine responses of CD19‐CAR T cells, whereas M11‐CAR T cells maintained strong responses. This effect was partially attributable to direct recognition of virion‐associated gB, resulting in activation of M11‐CARs.
Conclusions: M11‐CAR T cells enable MHC‐independent recognition of MCMV, providing a potential strategy to circumvent CMV‐mediated disruption of antigen presentation and immune recognition. Our findings demonstrate that virions can directly shape virus‐specific CAR T‐cell responses and highlight the importance of antigen recognition mechanisms that are independent of MHC presentation. This provides a basis for refining CAR designs for persistent viral infections characterized by immune evasion.
Related
- Cytomegalovirus Infection Is Associated with Accelerated Murine Glioblastoma Progression and Alterations in the Tumor Microenvironment
- Cytomegalovirus Viremia Is Strongly Associated With 6-Month Mortality Among Adults Living With Advanced HIV Disease: A Prospective Cohort Study in South Africa
- An Active Cytomegalovirus Infection and Epstein-Barr Virus Reactivation Complicated by Cytomegalovirus Meningitis and Virus-Associated Hemophagocytic Lymphohistiocytosis during Methotrexate and Upadacitinib Therapy in a Patient with Rheumatoid Arthritis
- Nutritional Status in Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease
- Myelin Oligodendrocyte Glycoprotein Antibody Associated with Lumbar Radiculitis: A Case Report
BibTeX
@article{kubel2026m11car,
title = {{M11‐CAR T cells inhibit murine cytomegalovirus in vitro upon recognition of virion‐ and cell‐associated glycoprotein B}},
author = {Sabrina Kübel and Christopher Garçon and Hanna Menschikowski and Arne Cordsmeier and Jens‐Christian Albrecht and Friederike Oltmanns and Larissa Bauer and Manuel Hermann and Kristina Holdt and Heinrich Sticht and Marco Thomas and Thomas H Winkler and Brigitte Scholz and Doris Jungnickl and Armin Ensser},
journal = {Clinical \& Translational Immunology},
year = {2026},
month = nov,
doi = {10.1002/cti2.70128},
url = {https://doi.org/10.1002/cti2.70128},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - M11‐CAR T cells inhibit murine cytomegalovirus in vitro upon recognition of virion‐ and cell‐associated glycoprotein B
AU - Sabrina Kübel
AU - Christopher Garçon
AU - Hanna Menschikowski
AU - Arne Cordsmeier
AU - Jens‐Christian Albrecht
AU - Friederike Oltmanns
AU - Larissa Bauer
AU - Manuel Hermann
AU - Kristina Holdt
AU - Heinrich Sticht
AU - Marco Thomas
AU - Thomas H Winkler
AU - Brigitte Scholz
AU - Doris Jungnickl
AU - Armin Ensser
PY - 2026
DA - 2026/11/03
JO - Clinical & Translational Immunology
DO - 10.1002/cti2.70128
UR - https://doi.org/10.1002/cti2.70128
AB - Objectives: Viral infections are predominantly managed with conventional antiviral drugs, which, despite their efficacy, can cause toxicity and promote resistance. Cell‐based immunotherapies offer an alternative, but cytomegaloviruses (CMV) profoundly interfere with MHC class I antigen presentation, thereby impairing conventional virus‐specific T‐cell responses towards infected cells. We therefore aimed to develop an MHC‐unrestricted CAR T‐cell approach for CMV infection and investigate its antiviral activity. Methods: We generated M11‐CAR, a fully murine, second‐generation CAR based on the M11 monoclonal antibody targeting glycoprotein B (gB) of murine CMV (MCMV). Primary splenocytes were transduced to assess CAR functionality following ectopic gB expression or MCMV infection. T‐cell cytotoxicity, cytokine production and antiviral activity were evaluated and compared with human CD19‐specific control CAR T cells. Results: M11‐CAR T cells specifically recognized gB following ectopic expression and MCMV infection, inducing cytotoxicity and cytokine production. CAR‐mediated cytokine production, particularly interferon‐γ, translated into robust MCMV inhibition. Increasing MCMV loads impaired cytokine responses of CD19‐CAR T cells, whereas M11‐CAR T cells maintained strong responses. This effect was partially attributable to direct recognition of virion‐associated gB, resulting in activation of M11‐CARs. Conclusions: M11‐CAR T cells enable MHC‐independent recognition of MCMV, providing a potential strategy to circumvent CMV‐mediated disruption of antigen presentation and immune recognition. Our findings demonstrate that virions can directly shape virus‐specific CAR T‐cell responses and highlight the importance of antigen recognition mechanisms that are independent of MHC presentation. This provides a basis for refining CAR designs for persistent viral infections characterized by immune evasion.
SN - 2050-0068
ER -