ArticleBMC cancer2013
Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01800812 (Phase One Study With Direct Individual Benefit), which is not on this map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase One Study With Direct Individual Benefit: Effects of OM-174 in Adult Patients With Solid Tumors.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Contribution of TLR4 to colorectal tumor microenvironment, etiology and prognosis.Journal of cancer research and clinical oncology · 2023Pooled it
- A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice.Archives of virology · 2024Article
- Radiotherapy Combined with Intralesional Immunostimulatory Agents for Soft Tissue Sarcomas.Seminars in radiation oncology · 2024Review
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- Manufacturing-dependent change in biological activity of the TLR4 agonist GSK1795091 and implications for lipid A analog development.Clinical and translational science · 2022Article
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.BioImpacts : BI · 2022Review
- Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity.Cancer treatment and research · 2022Article
- Beyond PD-1: The Next Frontier for Immunotherapy in Melanoma.Frontiers in oncology · 2021Review
- Review
- The Role of Toll-Like Receptors in Oncotherapy.Oncology research · 2019Review
- A nanoparticle-based approach to improve the outcome of cancer active immunotherapy with lipopolysaccharides.Drug delivery · 2018Article
- Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid A treatment.Oncotarget · 2018Article
- An efficient and scalable synthesis of potent TLR2 agonistic PAMRSC advances · 2018Article
- TLR4/IFNγ pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models.Oncoimmunology · 2016Article
- Toll-like receptors: the swiss army knife of immunity and vaccine development.Clinical & translational immunology · 2016Review
- Dysregulation of signaling pathways associated with innate antibacterial immunity in patients with pancreatic cancer.Central-European journal of immunology · 2016Review
- Senescence of tumor cells induced by oxaliplatin increases the efficiency of a lipid A immunotherapy via the recruitment of neutrophils.Oncotarget · 2014Article
- Review
- Toll-like receptor signaling regulates cisplatin-induced mechanical allodynia in mice.Cancer chemotherapy and pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was conducted to determine the maximum tolerated dose, the recommended phase II dose and biological response associated with OM-174 administered as intravenous infusion.
methodsPatients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 μg/m(2). Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed.
resultsSeventeen patients were included. The highest dose administered was 1000 μg/m(2) repeated in 15 injections. The most common toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 μg/m(2) of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks of TNF-alpha and IL-6 concentrations were detected after the first infusion and decreased progressively suggesting tolerance.
conclusionOM-174 therapy was well tolerated at biologically active concentrations. Whereas the recommended dose was not determined, further studies are planned in combination with chemotherapy as animal models suggest a strong synergistic antitumor effect.
trial registrationNCT01800812 (ClinicalTrials.gov Identifier).
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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.