Retargeting of viruses to generate oncolytic agents

Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal
tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their
tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently
employed to specifically redirect viruses towards surface receptors on tumor cells. Threemajor strategies can be distinguished; they
involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral
surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus
to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are
given. Because of their potential to cause sustained, multiround infection—a desirable characteristic for eradicating tumors—
particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter
protein.