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TruCulture

Case Studies

 See examples of TruCulture utilized in various clinical trials. 
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TruCulture has been utilized in dozens of clinical trials with demonstrated utility in understanding innate immunity, evaluating immune response to oncology treatments, understanding longitudinal changes in immunity and vaccine development. Open the case studies below for an overview of different studies that utilized TruCulture.

 

Below the case studies is a bibliography of publications that utilized TruCulture.

Restoration of innate immune function in chronic lymphocytic leukemia (CLL)

Chroniclymphocytic leukemia (CLL) is a cancer of mature B cells associated with immune dysregulation.

 

A 2024 study examined the innate immune function in chronic lymphocytic leukemia (CLL) patients treated with acalabrutinib or ibrutinib + venetoclax. The study utilized TruCulture tubes to assess cytokine release in response to standardized stimuli and characterized innate immune phenotypes via flow cytometry. At baseline, patients exhibited impaired cytokine responses and elevated pro-inflammatory cytokines.

 

However, after two to three cycles of targeted therapy, these responses normalized, correlating with a decrease in infection duration and frequency. The study highlights the potential of targeted treatments to restore innate immune function and reduce infection risk in CLL patients, with ongoing investigations in the PreVent-ACaLL phase 2 trial.

 

It also underscores the crucial role of TruCulture tubes in providing a standardized method to assess innate immune function, ensuring consistent and reliable measurement of cytokine responses.

 

Reference: Svanberg Teglgaard R, Marquart HV, HartlingHJ, Bay JT, da Cunha-Bang C, Brieghel C, et al. Improved innate immune functionin patients with chronic lymphocytic leukemia treated with targeted therapy inclinical trials. Clin Cancer Res. 2024;30(9):1959-1971. Available from: https://doi:10.1158/10780432.CCR-23-2522

Tailoring non-small cell lung cancer (NSCLC) treatment, including PD-L1 immune checkpoint inhibitors

In an open-label clinical study, 37 patients with inoperable non-small cell lung cancer (NSCLC) were observed to evaluate the immune response to different treatments, including PD-L1 immune checkpoint inhibitors (ICI), chemotherapy (CT), and chemo-radiotherapy (CT/RT).

 

Blood samples were collected at several intervals and immune responses were analyzed using TruCulture tubes and a standardized immunoassay. TruCulture enabled precise monitoring of cytokine release as a measure of immune function for both intracellular and extracellular pathways, with researchers identifying an evolving immune response triggered by both immune checkpoint inhibitors and chemotherapy.

 

Higher cytokine levels were observed prior to therapy and lower cytokines were observed after therapy, suggesting immune activation. The immune response from patients receiving chemotherapy correlated with 12-month survival, suggesting the prognostic value of this method.

 

These results indicate that TruCulture maybe an effective tool for early evaluation of response to immune check point inhibitors in NSCLC and other cancers, emphasizing the critical role of timing and understanding of immune function for precise immunomonitoring.

 

Reference: Ryssel H, Egebjerg K, Nielsen SD, LundgrenJ, Pøhl M, Langer SW, et al. Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer. Front Immunol. 2022;13:1024224. Available from: https://doi:10.3389/fimmu.2022.1024224 

RIPK1 inhibition in inflammatory diseases

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in mediating necroptosis, a form of programmed necrosis implicated in various inflammatory diseases, including rheumatoid arthritis and psoriasis. GSK2982772, a selective RIPK1 inhibitor, has shown promise in preventing RIPK1-mediated cell death and cytokine production.

 

Researchers used TruCulture tubes to determine the pharmacodynamics (PD) of single and repeated doses of GSK2982772 in healthy adult males. TruCulture tubes were supplemented with a cocktail (TNF-αα, zVAD, and Smac mimetic) to stimulate necroptosis.

 

Volunteers received, across 14 days:

1) placebo,

2) 20mg once daily,

3) 60mg once daily,

4) 60mg twice daily, or

5) 120mg twice daily.

 

Whole blood samples collected at multiple time points were incubated in TruCulture tubes. Supernatants analyzed for MIP-1αα production demonstrated that GSK2982772 inhibited RIPK1-dependent MIP-1αα production, with maximum inhibition observed at 1.5- and 8-hours post-treatment across all dosing groups.

 

This study demonstrated TruCulture’s effectiveness in assessing pharmacodynamic responses.

 

Reference: Weisel K, Scott NE, Tompson DJ, Votta BJ, Madhavan S, Povey K, et al. Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers. Pharmacol Res Perspect. 2017 Dec;5(6):e00365. Available from: https://doi.org/10.1002/prp2.365

Enhancing anti-cancer immunity through NK cell modulation

Natural killer (NK) cell activation and killing of tumor cells are important innate responses in anti-cancer immunity. Modulating NK cell function by stimulating to ll-like receptors has been shown to enhance therapeutic efficacy of biologics. VTX-2337 is a TLR-8 agonist that activates NK cells by enhancing antibody dependent cell-mediated cytotoxicity in the presence of other clinical therapeutics (trastuzumab, rituximab, cetuximab).

 

In a 2016 study, whole blood was collected from healthy donors using TruCulture tubes containing 2 concentrations of VTX-2337 (0.3 or 1 μM) and incubated for 24 hours. Supernatant analysis showed that VTX-2337 stimulated IL-18 and IL-1ββ production, indicating cytokine production via TLR-8 engagement.

 

These results demonstrate the potential of VTX-2337 to boost anti-cancer immunity and highlight TruCulture’s advantage in studying immune responses.

 

Reference: Dietsch GN, Lu H, Yang Y, Morishim C, ChowLQ, Disis ML, et al. Coordinated activation of toll-like receptor8 (TLR8) andNLRP3 by the TLR8 agonist, VTX-2337, ignites tumoricidal natural killer cellactivity. PLOS One. Feb 29, 2016. Available from: https://doi.org/10.1371/journal.pone.0148764

Impact of smoking on immune responses

In a 2024 study published in Nature, researchers explored factors contributing to variability in immune responses.

 

Researchers examined 136 variables and identified smoking, latent cytomegalovirus infection, and body mass index as major contributors to cytokine response variability, comparable to age, sex and genetics.

 

Whole blood samples from 1,000 healthy donors were collected and stimulated using TruCulture tubes with various immune agonists, and cytokine levels were measured using our internally developed Luminex-based assays.

 

Smoking was found to influence cytokine secretion, affecting both innate and adaptive immune responses. While the impact on innate responses diminishes rapidly after quitting smoking, the effect on adaptive responses remains long after cessation and is tied to epigenetic memory.

 

The study identified specific cytokines and immune responses affected by smoking, including associations with plasma levels of CEACAM6 and DNA methylation changes. The findings reveal that smoking has both short- and long-term effects on immune responses, with potential clinical implications for the risk of developing infections, cancers or autoimmune diseases.

 

TruCulture tubes provided a controlled environment for accurately assessing these immune responses.

 

Reference: Saint-André V, Charbit B, Biton A, RouillyV, Possémé C, Bertrand A, et al. Smoking changes adaptive immunity withpersistent effects. Nature. 2024;626(8000):827-835. Available from: https://doi:10.1038/s41586-023-06968-8

Safety and immunogenicity of SARS-CoV-2 vaccines

In this study, TruCulture tubes were used as a standardized whole‑blood stimulation system to assess antigen‑specific T‑cell responses after two doses of an adjuvanted SARS‑CoV‑2 recombinant protein vaccine.

 

Blood samples collected at multiple time points were drawn directly into three types of TruCulture tubes:

- spike‑antigen tubes

- negative‑control tubes

- positive‑control tubes (SEB + CD28)

to measure cytokine secretion profiles ex vivo.

 

Using TruCulture provided high‑fidelity immune response readouts, enabling the researchers to profile Th1‑associated cytokines (IFN‑γ, IL‑2, TNF‑α), which increased after vaccination. TruCulture minimized pre-analytical variability, enabled high-throughput immune profiling at our lab, and differentiated between immune signatures, enabling clear comparison of cytokine profiles across vaccine arms and timepoints.

 

Reference: Goepfert PA, Fu B,Chabanon AL, et al. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. Lancet Infect Dis.2021;21(9):1257-1270. doi:10.1016/S1473-3099(21)00147-X 

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Early changes in immune, coagulation, and organ function after clinical and experimental polytrauma (2019) Halbgbauer Repositorium der Universit?t Ulm
Exploring and redefining Autoimmune polyendocrine syndrome type 1 (2019) Bruserud Skipnes Kommunikasjon, University of Bergen
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Type I Interferon Predicts an Alternate Immune System Phenotype in Systemic Lupus Erythematosus (2019) Thanarajasingam U, Muppirala AN, Jensen MA, Ghodke-Puranik Y, Dorschner JM, Vsetecka DM, Amin S, Makol A, Ernste F, Osborn T, Moder K, Chowdhary V, Niewold TB ACR Open Rheumatology
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Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers (2020) Schubauer-Berigan MK, Dahm MM, Toennis CA, Sammons DL, Eye T, Kodali V, Zeidler-Erdely PC, Erdely A Nanotoxicology
Application of the TruCulture? whole blood stimulation system for immune response profiling in cattle (2020) OBrien MB, McLoughlin RM, Meade KG Veterinary Immunology and Immunopathology
Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial. (2020) Recourt K, van der Aart J, Jacobs G, de Kam M, Drevets W, van Nueten L, Kanhal K, Siebenga P, Zuiker R, Ravenstijn P, Timmers M, van Gerven J, de Boer P Journal of Psychopharmacology
Systematic investigation of polyurethane biomaterial surface roughness on human immune responses in vitro (2020) Segan S, Jakobi M, Khokhani P, Klimosch S, Billing F, Schneider M, Martin D, Metzger U, Biesemeier A, Xiong X, Mukherjee A, Steuer H BioMed Research International
Innate Immune Stimulation of Whole Blood Reveals IFN-1 Hyper-Responsiveness in Type 1 Diabetes (2020) Rodrigues KB, Dufort MJ, Llibre A, Speake C, Jubayer Rahman M, Bondet V, Quiel J, Linsley PS, Greenbaum CJ, Duffy D, Tarbell KV Diabetologia
Systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome due to a CASP1 variant causing inflammasome hyperactivation (2020) Jorgensen SE, Christiansen M, Host C, Glerup M, Mahler B, Lausten MM, Gad HH, Hartmann R, Herlin T, Mogensen TH Rheumatology
Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotaxemia versus ex vivo stimulation (2020) Tawfik DM, Lankelma JM, Vachot L, Cerrato E, Pachot A, Wiersinga WJ, Textoris J Scientific Reports
Towards standardization of immune functional assays (2020) Mouton W, Albert-Vega C, Boccard M, Bartolo F, Oriol G, Lopez J, Pachot A, Textoris J, Mallet F, Brengel-Pesce K, Trouillet-Assant S Clinical Immunology
Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium bacillus calmette guerin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy (2020) Rentsch CA, Bosshard P, Mayor G, Rieken M, Puschel H, Wirth G, Cathomas R, Parzmair GP, Grode L, Eisele B, Sharma H, Gupta M, Gairola S, Shaligram U, Goldenberger D, Spertini F, Audran R, Enoui M, Beradi S, Hayoz S, Wicki A Oncoimmunology
Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial (2020) Rahmel T, Hubner M, Koos B, Wolf A, Willemsen KM, Straub G, Effinger D, Adamzik M, Kreth S BMJ Open
Preoperative TruCulture whole blood cytokine response predicts postoperative inflammation in pancreaticoduodenectomy patients - a pilot cohort study (2020) Aasvang EK, Pitter S, Hansen CP, Storkholm JH, Krohn PS, Burgdorf SK, Von Stemann JH, Lundgren JD, Nielsen SD, Kehlet H, Ostrowski SR Scandinavian Journal of Immunology
Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study (2020) Genovese MC, Gaylis NB, Sikes D, Kivitz A, Horowitz DL, Peterfy C, Glass EV, Levine YA, Chernoff D The Lancet Rheumatology
Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,30dioxygenase 2, in patients with advanced solid tumors (2020) Naing A, Eder JP, Piha-Paul SA, Gimmi C, Hussey E, Zhang S, Hildebrand V, Hosagrahara V, Habermehl C, Moisan J, Papadopoulos KP Journal for ImmunoTherapy of Cancer
First-in-human, single- and multiple-ascending dose studies in healthy subjects to assess pharmacokinetics, pharmacodynamics, and safety/tolerability of iberdomide, a novel cereblon E3 ligase modulator (2020) Ye Y, Gaudy A, Schafer P, Thomas M, Weiss D, Chen N, Liu L, Xue Y, Carayannopoulos L, Palmisano M Clinical Pharmacology in Drug Development
Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study (2020) Albert Vega C, Oriol G, Bartolo F, Lopez J, Pachot A, Rimmele T, Venet F, Leray V, Monneret G, Delwarde B, Brengel-Pesce K, Textoris J, Mallet F, Trouillet-Assant S Scientific Reports
Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection (2020) Duffy D, Nemes E, Llibre A, Rouilly V, Musvosvi M, Smith N, Filander E, Africa H, Mabwe S, Jaxa L, Charbit B, Mulenga H, the Milieu Interieur Consortium, Tameris M, Walzl G, Malherbe S, Thomas S, Hatherill M, Bilek N, Scriba TJ, Albert ML Clinical Infectious Diseases
Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial (2020) Aranow C, Atish-Fregoso Y, Lesser M, Mackay M, Anderson E, Chavan S, Zanos TP, Datta-Chaundhuri T, Bouton C, Tracey KJ, Diamond B Annals of the rheumatic diseases
Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo (2020) Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermuller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot G, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S, Milieu interieur Consortium, Sellam J, Berenbaum F, Miceli C, Dougados M, Bianchi E, Rogge L Ann Rheum Dis
Characterization of LY2775240, a selective phosphodiesterase-4 inhibitor, in nonclinical models and in healthy subjects (2020) Patel DR, Urva S, Ho S, Buckman CJ, Ma Y, Lim J, Sissons SE, Zuniga MS, Philips D, Cox K, Dairaghi D Clinical and Translational Science
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Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes (2021) Stein MM, Conery M, Magnaye KM, Clay SM, Billstrand C, Nicolae R, Naughton K, Ober C, Thompson EE Scientific Reports
First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of ALPN-101, a dual CD28/ICOS antagonist, in healthy adult subjects (2021) Yang J, Lickliter JD, Hilson JL, Means GD, Sanderson RJ, Carley K, Tercero A, Manjarrez KL, Wiley JR, Peng SL Clinical and Translational Science
Novel approaches to develop biomarkers predicting treatment responses to TNF-blockers (2021) Mezghiche I, Yahia-Cherbal H, Rogge L, Bianchi E Expert Review of Clinical Immunology
Machine learning-based single cell and integrative analysis reveals that baseline mDC predisposition predicts protective Hepatitis B vaccine response (2021) Aevermann B, Shannon CP, Novotny M, Ben-Othman R, Cai B, Zhang Y, Ye JC, Kobor MS, Gladish N, Lee A, Blimke TM, Hancock RE, Llibre A, Duffy D, Koff WC, Sadarangani M, Tebbutt SJ, Kollmann TR, Scheuermann RH medRxiv
Novel signatures associated with systemic lupus erythematosus clinical response to IFN-a/-? inhibition (2021) Seridi L, Cesaroni M, Orillion A, Schreiter J, Chevrier M, Marciniak S, Migone TS, Stohl W, Chatham WW, Furie RA, Benson J, Jordan J Lupus
Primary human dendritic cells and whole-blood based assays to evaluate immuno-modulatory properties of heat-killed commensal bacteria (2021) Norton JE Jr., Kommineni S, Akrivoulis P, Gutierrez DA, Hazuda DJ, Swaminathan G Vaccines
Differential response induced by LPS and MPLA in immunocompetent and septic individuals (2021) Vega CA, Karakike E, Bartolo F, Mouton W, Cerrato E, Brengel-Pesce K, Giamarellos-Bourboulis EJ, Mallet F, Trouillet-Assant S Clinical Immunology
Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults (2021) van Hoffen E, Mercenier A, Vidal K, Benyacoub J, Schloesser J, Kardinaal A, Lucas-van de Bos E, van Alen I, Rogero I, Duintjer K, Berendts A, Albers R, Kleerebezem M, Bruggencate ST Scientific Reports
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CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-infammatory cytokine production (2022) Rajula Gaur, Kofi A Mensah, Jason Stricker, Mary Adams, Anastasia Parton, Dorota Cedzik 1, Jamie Connarn 1, Michael Thomas, Gerald Horan, Peter Schafer, Stuart Mair, Maria Palmisano, Francisco Ram?rez-Valle Arthritis Research and Therapy
Exploration of the induced cytokine responses in European Lyme neuroborreliosis: A longitudinal cohort study (2022) Rosa Maja M?hring Gynthersen, Mathilde Orbaek, Helene Mens, Christian Stenor, Lothar Wiese, Sisse Rye Ostrowski, Susanne Dam Nielsen, Anne-Mette Lebech Ticks and Tick-borne Diseases
Distinct Immune Reconstitution Profiles Captured by Immune Functional Assays at 6 Months Post Allogeneic Hematopoietic Stem Cell Transplantation (2022) William Mouton, Anne Conrad, Vincent Alcazer, Mathilde Boccard, Maxime Bodinier, Guy Oriol, Fabien Subtil, Helene Labussiere-Wallet, Sophie Ducastelle-Lepretre, Fiorenza Barraco, Marie Balsat, Gaelle Fossard, Karen Brengel-Pesce, Florence Adler, Sophie Trouillet-Assant Transplantation and Cellular Therapy
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Early and recent exposure to adversity, TLR-4 stimulated inflammation, and diurnal cortisol in women with interstitial cystitis/bladder pain syndrome: A MAPP research network study (2023) Susan K Lutgendorf, Sharaf Zia, Yi Luo, Michael ODonnell, Adrie van Bokhoven, Catherine S Bradley, Robert Gallup, Jennifer Pierce, Bayley J Taple, Bruce D Naliboff, J Quentin Clemens, Karl J Kreder, Andrew Schrepf Brain, Behavior, and Immunity
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Autoantibodies to Variable Heavy (VH) Chain Ig Sequences in Humans Impact the Safety and Clinical Pharmacology of a VH Domain Antibody Antagonist of TNF-a Receptor 1 (2013) Holland MC, Wurthner JU, Morley PJ, Birchler MA, Lambert J, Albayaty M, Serone AP, Wilson R, Chen Y, Forrest RM, Cordy JC, Lipson DA, Bayliffe AI Journal of Clinical Immunology, July 2013
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