Abstract
Clinical success in the therapeutic targeting of the CD47 signaling pathway has thus far remained elusive despite a promising scientific rationale. Use of oncolytic viruses to deliver CD47 targeting agents represents a novel approach to modulate the immunological landscape of the tumor microenvironment and to generate a systemic antitumor immune response. In recent preclinical studies, an oncolytic herpes simplex virus-1 engineered to express an inhibitory CD47-binding nanobody demonstrated promising antitumor activity. Several other oncolytic viruses engineered to express CD47 inhibitory molecules are also in preclinical development. Oncolytic viruses have the potential to mitigate drug delivery issues and may avoid systemic toxicities that have limited conventional CD47 targeting therapeutics. These novel therapeutics warrant further evaluation in clinical trials. The potential advantages, limitations, and remaining critical questions regarding this strategic approach are discussed here.