Abstract
Human cytomegalovirus (HCMV), by primary infection or reactivation, represents a great risk for immune-suppressed or compromised patients. In immunocompetent humans, the immune system suppresses the spread of HCMV during an infection, resulting in a mostly asymptomatic or mild course of the disease, whereas in immune suppressed patients, the compromised host immune response cannot control the viral infection. Multiple viral immunomodulatory mechanisms additionally contribute to immune evasion. Use of chimeric antigen receptors (CARs), a treatment strategy adapted from cancer immunotherapy, is investigated for possible application to combat HCMV and other infections in immunocompromised patients. The administration of CAR+ T-cells directed against HCMV antigens can bypass viral immune evasion and may complement existing treatment methods. This review gives a short overview of HCMV, the obstacles of current treatment options as well as a brief introduction to CARs and the current research situation on CAR+ T-cells against HCMV.
Highlights
Human cytomegalovirus (HCMV), by primary infection or reactivation, represents a great risk for immune-suppressed or compromised patients
Viral Fc receptors (FcRs), three in HCMV, and more than one in murine cytomegalovirus (MCMV), are expressed on the surface of infected cells, which compromise antibody-dependent cellular cytotoxicity (ADCC) by the binding of the Fc domain of host antibodies to viral FcRs [7]
HCMV-infected a particular variety of heterogeneous viral glycoprotein complexes (GC), including of the oligomer gB (GC I), the heterodimer gN/gM. Glycoprotein complexes on their surface, which may serve as potential targets for chimeric antigen receptors (CARs)(GC II), the heterotrimer gH/gL/gO (GC III) as well as the so-called pentameric complex immunotherapy.(PC)
Summary
Human cytomegalovirus (HCMV) is a highly prevalent pathogen, infecting the majority of the adult population followed by lifelong persistence in the host. Recent studies have shown that administration of CMV-specific T-cells (CMVSTs) from a carefully selected pool of third-party donors with an HLA match of only 2 out of 8 can result in a strong antiviral response [10]. These findings allow cryopreserved ‘cell banks’ to be manufactured, at least in the case of common HLA profiles, resulting in an off-the-shelf treatment option for serious CMV-infections. CARs that retarget the specific cytolytic potential of cytotoxic T-cells, and have proven their efficacy in cancer immunotherapy, are the focus of this review
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