Work

M11 ‐ CAR T cells inhibit murine cytomegalovirus in vitro upon recognition of virion‐ and cell‐associated glycoprotein B

Year: 2026

Type: article

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.

Source: Clinical & Translational Immunology

DOI: 10.1002/cti2.70128