The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system
Open accessAbstract
Toll-like receptor (TLR) ligation activates both the innate and adaptive immune systems, and plays an important role in antiviral and anti-tumor immunity. Therefore, a significant amount of effort has been devoted to exploit the therapeutic potential of TLR agonists. Depending on the therapeutic purpose, either as adjuvants to vaccine, chemotherapy or standalone therapy, TLR agonists have been administered via different routes. Both preclinical and clinical studies have suggested that the route of administration has significant effects on pharmacokinetics, and that understanding these effects is critical to the success of TLR agonist drug development. This article will summarize the pharmacokinetics of TLR agonists with different administration routes, with an emphasis on clinical studies of TLR ligands in oncologic applications.
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The connection density of the network model (27.3%) is in line with reported estimates of connectivity in protein signaling networks.
“The connection density of our network model (27.3%) is in line with reported estimates of connectivity in protein signaling networks46.”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [46]
The passages on TLR agonist pharmacokinetics and targeted delivery (Systemic administration of TLR agonists; no page provided) do not discuss protein-signaling network connectivity. Searches for “connection density 27.3%” and “connectivity network model” found no estimate against which to compare the citing authors’ model. (LLM, conf=0.76)
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- Authors
- Engel, A. L., Holt, G. E., & Lu, H.
- Affiliations
- Bastyr University (US)
- University of Miami (US)
- University of Washington (US)
- Corresponding author
- Lu, Hailing
- Venue
- Expert Review of Clinical Pharmacology
- Publisher
- Informa UK Limited
- Published
- 2011-03
- Volume
- 4
- Issue
- 2
- Pages
- 275-289
- ISSN
- 1751-2433 (ISSN-L)
- 1751-2441
- PMC
- PMC3105468
- OpenAlex
- W2088599017
- Cited by
- 205
- References
- 121
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 22 · 2023: 16 · 2022: 30 · 2021: 19 · 2020: 17 · 2019: 20 · 2018: 16 · 2017: 10 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 8
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Review of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P30HL101321)
- National Cancer Institute (R01CA138547)
- National Center for Complementary and Integrative Health (T32AT000815)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- TLR agonists, pharmacokinetics, route of administration, vaccine adjuvants, cancer immunotherapy, innate immunity, adaptive immunity, antiviral immunity, antitumor immunity, clinical pharmacology
- MeSH terms
- Adjuvants, Immunologic, Animals, Clinical Trials as Topic, Humans, Immune System, Ligands, Signal Transduction, Drug Delivery Systems, Toll-Like Receptors
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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