Study in mice significantly slowed tumor growth and activated anti-tumor immune response

Researchers at the University of Missouri School of Medicine have discovered a specific combination immunotherapy that shows promise in the fight against liver cancer.

The therapy involves a tumor-suppressing lipid molecule called nanoliposome C6-ceramide (LipC6) and an antibody against cytotoxic T cell antigen 4 (CTLA4). When used together in this study, LipC6 and the anti-CTLA4 antibody significantly slowed tumor growth and improved the strength of tumor-attacking T cells.

“Our analysis revealed that combination therapy significantly extended the lifespan of tumor-bearing mice compared to mice with only one type of therapy or no therapy at all,” said co-lead researcher Guangfu Li, PhD, DVM , Associate Professor in the Department of Surgery and Department of Molecular Microbiology and Immunology.

Li said the finding is especially promising given the current lack of effective therapies for liver cancer, which is the third leading cause of cancer-related death in the United States. For patients diagnosed with liver cancer, the average five-year survival rate of all stages is 20%, according to the American Cancer Society.

“What is particularly remarkable is that we have now demonstrated that LipC6 treatment significantly improves the ability of anti-CTLA-4 antibodies to suppress liver cancer,” Li said. -CTLA-4 have been approved by the FDA for use in human patients, so this combination treatment can be quickly translated into clinical application.”

Further research will be needed to better understand the mechanisms underlying the success of this combination.

“The human therapeutic response to another commonly used type of immunotherapy, anti-PD-1, is only about 14% in patients with liver cancer,” said the co-investigator. principal Kevin F. Staveley-O’Carroll, MD, PhD, professor in the Department of Surgery. “We also tested anti-PD-1 immunotherapy in combination with LipC6, but it showed no benefit over the robust response demonstrated by the combination of LipC6 and anti-CTLA4 antibodies. This represents an approach new and powerful therapy.”

In addition to Li and Staveley-O’ Carroll, other MU co-authors include Xiaoqiang Qi, PhD, assistant research professor; Feng Wu, PhD, post-doc; Jussuf Kaifi, MD, assistant professor of surgery; Eric Kimchi, MD, chief of the division of surgical oncology and general surgery; and Sung Hoon Kim, visiting scholar from South Korea.

Their study, “C6-Ceramide nanoliposome in combination with anti-CTLA4 antibody enhances anti-tumor immunity in hepatocellular cancer,” was recently published by the journal Federation of American Societies for Experimental Biology. The research reported in this publication was supported by a grant from the National Cancer Institute of the National Institutes of Health. The content is the sole responsibility of the authors and does not necessarily represent the official views of the funding bodies.

Highlighting the promise of personalized healthcare and the impact of large-scale interdisciplinary collaboration, the NextGen Precision Health initiative brings together innovators from the University of Missouri and three other research universities in the UM system in the pursuit of life-changing advances in precision health. It’s a collaborative effort to leverage Mizzou’s research strengths toward a better future for the health of Missourians and beyond. The Roy Blunt NextGen Precision Health building at MU anchors the overall initiative and expands collaboration between researchers, clinicians and industry partners in the cutting-edge research center.

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Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

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