Oncolytic adenovirus capsid (Ad capsid)

The oncolytic adenovirus capsid is the complex protein shell of an engineered adenovirus, typically derived from serotype 5 (Ad5), designed to selectively target and eliminate cancer cells. It is composed of major structural proteins including the hexon, penton base, and fiber, which are responsible for protecting the viral genome and facilitating host cell entry (Source: PubMed, PMID: 30634492). In oncolytic virotherapy, the capsid serves as the primary interface for tumor-specific targeting, often modified with ligands like RGD peptides to bypass the need for the Coxsackievirus and Adenovirus Receptor (CAR), which is frequently downregulated in advanced tumors (Source: NIH, PMC5835557). Once the capsid binds to the target cell, it undergoes a programmed disassembly process that enables endosomal escape and delivery of the viral DNA to the nucleus for replication. This replication leads to direct tumor cell lysis and the release of progeny virions and tumor antigens, stimulating a robust "cold-to-hot" immune microenvironment transition (Source: Nature Reviews Cancer, doi:10.1038/nrc.2016.4). Despite its therapeutic potential, the capsid is a major target for the host's immune system, where pre-existing neutralizing antibodies can significantly reduce the efficacy of systemic administration (Source: Wikipedia, Oncolytic virus). Consequently, current research focuses on "stealth" capsid modifications, such as PEGylation or the use of chimeric capsids, to improve circulation time and tumor delivery.

Other names

Adenoviral capsidAd5 capsidOncolytic viral vector shellAdenovirus coat protein complex

The capsid facilitates tumor-selective infection through receptor-mediated endocytosis, followed by endosomal escape and nuclear delivery of the viral genome, ultimately leading to oncolytic cell death and immune activation.