ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Cancer viroimmunotherapy platforms based on varicella-zoster virus and cytomegalovirus.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- The immunomodulatory role of human cytomegalovirus in cancer in the era of checkpoint immunotherapy.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade.Nature medicine · 2025Article
- Oncolytic cytomegaloviruses expressing EGFR-retargeted fusogenic glycoprotein complex and drug-controllable interleukin 12.Cell reports. Medicine · 2025Article
- Cytomegalovirus Reactivation Is Associated With Lower Rates of Hepatocellular Carcinoma Recurrence After Liver Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine.NPJ vaccines · 2024Article
- Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy.International journal of molecular sciences · 2024Article
- Oncolytic α-herpesvirus and myeloid-tropic cytomegalovirus cooperatively enhance systemic antitumor responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Blockade of trans PD-L1 interaction with CD80 augments antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- CD8 T Cell Vaccines and a Cytomegalovirus-Based Vector Approach.Life (Basel, Switzerland) · 2021Review
- Tumor Control by Cytomegalovirus: A Door Open for Oncolytic Virotherapy?Molecular therapy oncolytics · 2020Review
- STING Sensing of Murine Cytomegalovirus Alters the Tumor Microenvironment to Promote Antitumor Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Uncovering the Anticancer Potential of Murine Cytomegalovirus against Human Colon Cancer Cells.Molecular therapy oncolytics · 2020Article
- Vaccine Vectors Harnessing the Power of Cytomegaloviruses.Vaccines · 2019Review
- Murine Cytomegalovirus Infection of Melanoma Lesions Delays Tumor Growth by Recruiting and Repolarizing Monocytic Phagocytes in the Tumor.Journal of virology · 2019Article
- Fuel and brake of memory T cell inflation.Medical microbiology and immunology · 2019Review
- Vaccine vectors: the bright side of cytomegalovirus.Medical microbiology and immunology · 2019Review
- From Vaccine Vector to Oncomodulation: Understanding the Complex Interplay between CMV and Cancer.Vaccines · 2019Review
- Early primed KLRG1- CMV-specific T cells determine the size of the inflationary T cell pool.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8(+) T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8(+) T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8(+) T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8(+) T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.