Stine Sofie Frank Lende

CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy

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Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.

Original languageEnglish
Article number919097
JournalFrontiers in cellular and infection microbiology
Volume12
Number of pages11
ISSN2235-2988
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

Copyright © 2022 Lende, Pahus, Monrad, Olesen, Mahr, Vibholm, Østergaard, Søgaard, Andersen, Denton and Tolstrup.

    Research areas

  • Adjuvants, Immunologic, Animals, Biomarkers, Humans, Immunologic Factors/therapeutic use, Immunotherapy, Mice, Sialic Acid Binding Ig-like Lectin 1, Toll-Like Receptor 9/agonists

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