A research group led by Professor Keisuke Nimura and Noriko Ohta at the Gunma University Initiative for Advanced Research (GIAR) in Maebashi, Japan, has uncovered a new anti-tumor mechanism involving a lipid-transport protein called Apolipoprotein D (ApoD). Their study reveals that ApoD is a key factor behind the tumor-suppressing effects of a therapeutic agent based on non-replicating Sendai virus envelopes (HVJ-E).
In recent years, cancer immunotherapy has emerged as a promising treatment option alongside surgery, chemotherapy, and radiation. One major breakthrough—immune checkpoint inhibitors—has shown success even in hard-to-treat cancers. However, challenges remain, including the limited range of cancers that respond to such treatments.
The team had previously observed that injecting HVJ-E into tumors could slow cancer growth. When combined with immune-stimulating antibodies, it also reduced tumors in parts of the body not directly treated. Until now, the mechanism behind these effects was unclear. Their new study shows that HVJ-E causes cancer cells to produce ApoD. This protein alone can block signals that promote tumor growth. When combined with activated T cells, it also helps eliminate tumors at distant sites.
This discovery suggests a new pathway for developing broad-spectrum cancer immunotherapies that are not limited by cancer type—and may even be effective against metastatic cancers.
Figure: How HVJ-E and ApoD Suppress Tumors
HVJ-E stimulates ApoD production in cancer cells, blocking tumor growth. When paired with activated T cells, ApoD also helps shrink tumors at distant sites. (“Apod” in the image refers to Apolipoprotein D (ApoD).)
■Publication Details:
Title: HVJ-E links Apolipoprotein d to anti-tumor effects
Authors:
Airi Ishibashi1,10,Noriko Ohta2,10, Yuko Uegaki1, Hidefumi Suzuki3,Katsuya Fukino2, Yuuta Hisatomi1, Atsushi Tanemura4, Riuko Ohashi5, Koji Kitamura1,6, Kotaro Saga1, Yasuhide Yoshimura1, Satoko Inubushi1, Kyoso Ishida1,7, Yoko Ino8, Yayoi Kimura8, Kenjiro Sawada7, Tadashi Kimura7, Eiji Kiyohara4, Kosuke Yusa9, Hidehisa Takahashi3, Yasufumi Kaneda1, and Keisuke Nimura2,10,*
1 Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
2 Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
3 Department of Molecular Biology, Graduate School of Medical Science, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
4 Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
5 Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
6 Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
7 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
8 Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
9 Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
10 These authors contributed equally to this work
*, Corresponding author
Journal: Journal for ImmunoTherapy of Cancer
DOI: 10.1136/jitc-2024-011442
Publication date: June 19, 2025, 5:00 PM (PST) – corresponds to June 20, 2025, 10:00 AM (JST)
■Funding:
This work was supported by the Center for Medical Research and Education, Graduate School of Medicine, Osaka University; research equipment shared in the MEXT Project for promoting public utilization of advanced research infrastructure (program for supporting the introduction of the new sharing system) Grant Number JPMXS0420600124, Gunma University; AMED grant number 18cm0106341h0001, 23ym0126809j0002, 24ym0126809j0003, 25ym0126809j0004, and 25ama221343h0001; JSPS KAKENHI grant number JP21K19408, JP21H05158, JP21H05160 and JP24H00633; JST Program for co-creating startup ecosystem, Grant Number JPMJSF2319; MEXT Promotion of Distinctive Joint Research Center Program Grant Number JPMXP0724020288 at the Advanced Medical Research Center, Yokohama City University; research grants from Bristol-Myers Squibb, The Osaka Community Foundation, and Osaka University Entrepreneurship Development Grant; and in part by the Osaka University Program for the Support of Networking among Present and Future Researchers.
■Contact Information:
Professor Keisuke Nimura
Division of Gene Therapy Science
Gunma University Initiative for Advanced Research (GIAR)
Gunma University
Email: nimura [at] gunma-u.ac.jp
■Related Links
Gunma University Initiative for Advanced Research(GIAR) Division of Gene Therapy Science Dr.NIMURA Laboratory
Gunma University Press Release(Original/Japanese)
