A Novel Therapy for Melanoma and Prostate Cancer Using a Non-Replicating Sendai Virus Particle (HVJ-E)

Abstract

An alternative option to avoid such a risk is to use a non-replicating oncolytic virus [44]. We found that a non-replicating oncolytic virus (HVJ-E: hemagglutinating virus of Japanenvelope) is able to induce cancer cell-specific apoptosis and immunity [45]. The induction of apoptosis and activation of dendritic cells in vitro, and anti-tumor activity in vivo are similar to the wild-type hemagglutinating virus of Japan (also known as Sendai virus, HVJ) [45]. The hemagglutinating virus of Japan was discovered in Sendai, Japan, in the 1950s [46]. It is a paramyxovirus with a minus-strand RNA genome. The virus has fusogenic activity [47, 48], and is used to prepare hybridoma cells for the production of monoclonal antibodies, and heterokaryons for chromosome analysis [49-51]. The hemagglutinating virus of Japan-envelope is an inactivated HVJ particle [52]. It is manufactured by a process similar to that used for whole virus particle vaccines. Good manufacturing practice (GMP)-regulated processes have been established in their production for use in preclinical and clinical studies [53]. We conducted dose-setting efficacy studies for HVJ-E in a murine cancer model in which dosedependent anti-cancer activity was observed. We also conducted safety studies following good laboratory practices (GLP), including pharmacological safety studies and toxicokinetic (TK) studies in rats and monkeys, as part of an investigational new drug (IND) application. Osaka University Hospital is currently conducting two investigational clinical studies with HVJ-E for the treatment of advanced melanoma and castration-resistant prostate cancer (CRPC) [54-56]. These clinical trials are the first human studies for HVJ-E and will reveal the safety and efficacy of the non-replicating virus (HVJ-E). Virotherapy with a non-replicating oncolytic virus is a new approach that is anticipated to provide a new strategy for cancer therapy. 2. A new strategy for cancer therapy Most cancers are still incurable and new approaches are required to improve the efficacy of cancer treatments. However, conventional cancer therapies are problematic. Chemotherapy with anti-cancer agents is useful in achieving tumor regression. However, the immune system, which is important in the removal of residual cancer cells, is also suppressed by these agents (Figure 1). Therefore, surviving cancer cells and cancer stem cells (CSC) eventually acquire drug resistance, resulting in tumor relapse (Figure 1) [57]. Thus, chemotherapy with cytotoxic drugs does not generally result in the necessary eradication of cancer cells required for long-term survival. Immune therapies for cancer offer a new approach to cancer treatment, and several products, including sipuleucel-T, are currently approved in advanced countries [58, 59]. The aim of these therapies is the removal of cancers by the immune system. Numerous cancer immune therapies are currently under evaluation in clinical studies. However, these agents are not potent because of lack of cytotoxic effect on cancer cells (Figure 1).

Add-On Effect of Hemagglutinating Virus of Japan Envelope Combined with Chemotherapy or Immune Checkpoint Inhibitor against Malignant Pleural Mesothelioma: An In Vivo Study

“…In this situation, we focused our attention on hemagglutinating virus of Japan envelope (HVJ-E) as a preparation that can be expected to be effective in combination with chemotherapy or ICIs to further improve treatment outcomes. HVJ-E exerts its therapeutic effect by enhancing the cancer immune cycle through activation of antigen-presenting cells such as dendritic cells and macropahges [9], killing cancer cells by cytotoxic T cells and Natural killer cells [10,11], and inducing M1-type macropahges through diverse immune activatinon effects [12][13][14]. In combination with chemotherapy and ICIs, HVJ-E is expected to have a high antitumor effect.…”