Coxsackievirus and adenovirus receptor (CXADR) (CAR)

The Coxsackievirus and adenovirus receptor (CAR), encoded by the CXADR gene, is a 46 kDa type I transmembrane protein and a member of the immunoglobulin superfamily [18]. It is primarily localized at the tight junctions of epithelial and endothelial cells, where it functions as a homophilic cell adhesion molecule essential for maintaining tissue integrity and regulating paracellular permeability [3, 4]. CAR is most notably recognized as the primary cellular attachment receptor for group B coxsackieviruses and many adenoviruses, including the serotype 5 (Ad5) widely used in gene therapy and oncolytic virotherapy [2, 6]. In oncology, CAR serves as the entry point for oncolytic adenoviruses such as CG7870, which utilize their fiber knob domain to bind the receptor and initiate infection [5, 16]. However, the expression of CAR is often downregulated in advanced or metastatic tumors, which can limit the efficacy of these viral therapies and has led to the development of modified fiber knob variants [1, 13]. Beyond its role in infection, CAR is involved in cardiac development and the transmigration of leukocytes during inflammatory responses [7, 18]. Therapeutic strategies targeting CAR include the use of oncolytic viruses for cancer treatment and soluble CAR-Fc fusions to block viral infections like myocarditis [21, 23]. Safety concerns for CAR-targeted therapies include off-target effects in the heart and liver, as well as the sequestration of viral particles by CAR-expressing erythrocytes [9, 18].

Other names

CXADRCARHCARCoxsackie virus and adenovirus receptorIg-like cell adhesion moleculeCXADR Ig-like cell adhesion molecule

Viral attachment and receptor-mediated endocytosis; Competitive inhibition of viral binding; Downregulation of receptor expression