Exploring the potential of HVJ-E for cancer immunotherapy.

HVJ-Envelope (HVJ-E), an inactivated particle derived from the Hemagglutinating virus of Japan, represents a unique virus-based approach for cancer immunotherapy. Unlike replication-competent oncolytic viruses, which exert antitumor effects through viral propagation and tumor cell lysis, HVJ-E lacks replicative capacity and pathogenicity because its viral genome is fragmented. Conversely, although most non-replicative viral vectors are designed primarily as delivery vehicles, HVJ-E itself possesses intrinsic antitumor activity. By preserving the native viral structure and membrane-fusion capacity of the parental virus, HVJ-E enables fragmented viral genomes to enter target cells, thereby inducing antitumor immune activation and tumor cell death. Mechanistic studies have shown that HVJ-E promotes dendritic cell maturation, activates natural killer cells, and stimulates cytotoxic T lymphocytes, leading to systemic antitumor immunity. Clinical trials have demonstrated favorable safety profiles and encouraging signs of efficacy. Furthermore, reverse translational research has identified combination strategies with T cell co-stimulatory signaling and the apolipoprotein system as a downstream mediator that enhances sensitivity to immune attack. This review summarizes the historical development, mechanistic insights, and emerging therapeutic concepts of HVJ-E as a novel cancer immunotherapy platform. A comprehensive literature search was conducted using PubMed for articles related to HVJ-E and cancer published between 2002 and 2025.