Exploring the potential of HVJ-E for cancer immunotherapy.

Abstract

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. When viruses enter the human body, they move into cells and multiply. This can damage our cells and cause diseases like infections. Although viruses are usually harmful, their ability to enter cells can also be useful. Researchers are using this property to turn viruses into “carriers” that deliver cancer treatments into the body. To keep patients safe, scientists modify these viruses so they can still enter cells but can no longer multiply. These are used in cancer treatment as “non-replicative viral vectors.” HVJ-Envelope (HVJ-E) is one of these safe carriers, made from the Hemagglutinating Virus of Japan (HVJ). However, HVJ-E is not just a carrier. It can also kill cancer cells directly and stimulate the body’s defense system to recognize and destroy them. This means HVJ-E acts as a highly unique active therapeutic agent. Recently, clinical trials have tested HVJ-E in patients with skin cancer and other cancers. These studies show that HVJ-E can shrink tumors safely without causing major side effects.In this review, we explain how HVJ-E was first developed as a carrier, how its unique features as an anti-tumor weapon were discovered, and how researchers have improved it for cancer treatment, including its testing in clinical trials. Finally, we discuss the future of HVJ-E-based cancer therapies, highlighting the latest research on developing new treatments that strongly trigger the body‘s anti-tumor defense system to eliminate cancer cells effectively.