A New Metabolomics Platform to Enhance Cancer Therapy
For an increasing variety of cancers the survival rate for patients treated with immune checkpoint inhibitors is now well above standard treatments such as chemotherapy. Yet, the number of patients that respond well to immunotherapy remains often frustratingly low, while other patients develop resistance to immune therapy over time.
Not surprisingly, investments in research aimed at improving the outcome of cancer immunotherapy continues to grow. Literally thousands of clinical studies are presently testing various types of combination therapies aimed at enhancing the efficacy of anti PD-1 antibody treatments. An increasing number of studies is looking at metabolites as ways to improve the natural immune response. Other studies are attempting to identify biomarkers that can predict the outcome of cancer immunotherapy in individual patients.
Metabolic modulators are among the most promising candidates for combination therapy using immune checkpoint inhibitors. Identifying powerful metabolic modulators requires a better understanding of both cross-talk between metabolites and tumor cells and intracellular metabolism in immune and cancer cells.
The approach in metabolomics taken at CCII reflects the centers legacy of fundamental research. In a multi-year collaboration with Shimadzu, scientists at CCII have built a sophisticated analytics platform that uses advanced liquid chromatography–mass spectrometry (LCMS) to analyze a large number of metabolites and lipids from various biological samples, e.g. plasma/serum, immune cells, and tissues. The new platform uses a dual LCMS set-up with both reverse phase and hydrophilic interaction liquid chromatography to measure metabolite concentration in peripheral blood (see below figure).
Figure: Metabolomics and Lipidomics Platform at CCII
In order to enhance CCII’s metabolomics platform, Kazuhiro Sonomura, a scientist at Shimadzu corporation, joined the center as a Visiting Associate Professor in 2021. The focus of his research is to enhance CCII’s metabolomics platform and broaden its usability for scientists at the center as well as at Kyoto University.
CCII’s advanced mass spectroscopy platform allows scientists at the center to quantify hundreds of targeted metabolites in the peripheral blood of experimental animals or human patients and, subsequently, identify metabolites or lipids that correlate with disease progression under various treatment strategies. Metabolites or lipids that can be statistically correlated with disease progression are then selected for further investigation to shed light on possible interactions with immune cells and mechanisms or action.
The new platform has already been used in a number of fundamental and clinical studies.1) Further, a number of promising candidates for metabolic modulators are presently being investigated by CCII and a network of collaborators. Other studies are attempting to identify metabolite biomarkers that can predict the outcome of cancer immunotherapy in individual patients. 2)
References:
1) See e.g. Tanaka K, Chamoto K, Saeki S, Hatae R, Ikematsu Y, Sakai K, Ando N, Sonomura K, Kojima S, Taketsuna M, Kim YH, Yoshida H, Ozasa H, Sakamori Y, Hirano T, Matsuda F, Hirai T, Nishio K, Sakagami T, Fukushima M, Nakanishi Y, Honjo T, Okamoto I. Combination bezafibrate and nivolumab treatment of patients with advanced non-small cell lung cancer. Sci Transl Med. 2022 Dec 14;14(675):eabq0021. DOI: 10.1126/scitranslmed.abq0021.
2) See e.g. Hatae R, Chamoto K, Kim YH, Sonomura K, Taneishi K, Kawaguchi S, Yoshida H, Ozasa H, Sakamori Y, Akrami M, Fagarasan S, Masuda I, Okuno Y, Matsuda F, Hirai T, Honjo T. Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy. JCI Insight. 2020 Jan 30;5(2):e133501. DOI: 10.1172/jci.insight.133501.